CaseLOPD-13: 2 weeks diagnosis

HPOsFreeText: GAA activity 2.6 (nmol · h−1 · mg−1), Mean percentage of normal 3.7%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2051C>T (p.Pro684Leu)

ClinVar: 285821 https://www.ncbi.nlm.nih.gov/clinvar/variation/285821/

gnomAD: European (Non-Finnish) 1.631e-4, Overall 8.195e-5 http://gnomad.broadinstitute.org/variant/17-78087027-C-T

CaseAddInfo: Late Onset Pompe Disease

CaseLOPD-2: 2 weeks diagnosis

HPOsFreeText: GAA activity 3.2 (nmol · h−1 · mg−1), Mean percentage of normal 4.5%

GenotypingMethod: Newborn Screening Panels

Variant: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Patient is homozygous for the above variant

CaseLOPD-6: 32 years diagnosis

HPOsFreeText: GAA activity 3.6 (nmol · h−1 · mg−1), Mean percentage of normal 5.1%

CaseNotHPOs: HP:0003236 (Increased serum CK)

GenotypingMethod: Newborn Screening Panels

Variant: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Patient is homozygous for the above variant

CasePD/Pathogenic-5: 4 weeks diagnosis

HPOsFreeText: GAA activity 6.5 (nmol · h−1 · mg−1), Mean percentage of normal 9.1%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant2: NM_000152.4:c.2065G>A (p.Glu689Lys)

ClinVar: 4030 https://www.ncbi.nlm.nih.gov/clinvar/variation/4030/

gnomAD: East Asian 0.2355, Overall 0.05524 http://gnomad.broadinstitute.org/variant/17-78087041-G-A

Variant3: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Patient has one pseudodeficency allele and one pathogenic allele, Nomenclature claims Variant 1 and 2 are in cis

CaseLOPD-5: 2 weeks diagnosis

HPOsFreeText: GAA activity 3.1 (nmol · h−1 · mg−1), Mean percentage of normal 4.4%

GenotypingMethod: Newborn Screening Panels

Variant: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Patient is homozygous for the above variant

CaseLOPD-1: 3 weeks diagnosis

HPOsFreeText: GAA activity 3.2 (nmol · h−1 · mg−1), Mean percentage of normal 4.5%

GenotypingMethod: Newborn Screening Panels

Variant: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Patient is homozygous for the above variant

CaseLOPD-4: 28 years diagnosis

HPOsFreeText: GAA activity 3.4 (nmol · h−1 · mg−1), Mean percentage of normal 4.7%

CaseNotHPOs: HP:0003236 (Increased serum CK)

GenotypingMethod: Newborn Screening Panels

Variant: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Patient is homozygous for the above variant

CaseLOPD-7: 24 years diagnosis

CasePresentingHPOs: HP:0003236, HP:0012378, HP:0002910 (Increased serum CK, Fatigue, Elevated transaminases)

HPOsFreeText: GAA activity 4.0 (nmol · h−1 · mg−1), Mean percentage of normal 5.6%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

CaseLOPD-11: 8.3 years diagnosis

HPOsFreeText: GAA activity 2.0 (nmol · h−1 · mg−1), Mean percentage of normal 2.8%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Chromosomal code not provided

Variant2: NP_000143.2:p.Q743∗ 

ClinVar: N/A

gnomAD: N/A

CaseAddInfo: Late Onset Pompe Disease

CaseLOPD-12: 2 weeks diagnosis

HPOsFreeText: GAA activity 2.0 (nmol · h−1 · mg−1), Mean percentage of normal 2.8%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Chromosomal code not provided and typo likely

Variant2: NP_000143.2:p.V350 mol/L

ClinVar: N/A

gnomAD: N/A

CaseAddInfo: Late Onset Pompe Disease

Case#: Subject number 14, female, 58 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0001252 (Hypotonia)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.33 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.-32-13T>C

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 17, male, 64 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003326 (Myalgia), HP:0002015 (dysphagia)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.54 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.875A>G (p.Tyr292Cys)

Variant 2 ClinVarID: 370577

Variant 2 CAid: CA16041886

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 12, male, 52 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.48 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1889-1G>A

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA401369820

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 3, female, 9 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy)

CaseNotHPOFreeText: no biopsy

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.15 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1396_1397insG (p.Val466GlyfsTer?)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA627699396

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 16, male, 59 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.17 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.-32-13T>C

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 10, male, 46 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0002153 (hyperkalemia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.36 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.236_246delCCACACAGTGC (p.Pro79ArgfsTer13)

Variant 2 ClinVarID: 371302

Variant 2 CAid: CA16041880

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 8, female, 32 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.3 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13, female, 57 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

Variant 2 ClinVarID: 188484

Variant 2 CAid: CA198797

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2, female, 7 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy)

CaseNotHPOFreeText: no biopsy

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.12 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1396_1397insG (p.Val466GlyfsTer?)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA627699396

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9, female, 44 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress)

CaseHPOFreeText:

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.34 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2819C>A (p.Ser940Ter)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA401327757

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 6, male, 19 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.281_282delCT (p.Pro94ArgfsTer?)

Variant 2 ClinVarID: 370458

Variant 2 CAid: CA16041881

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 7, male, 31 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.27 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1655T>C (p.Leu552Pro)

Variant 2 ClinVarID: 279811

Variant 2 CAid: CA8815429

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case7HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 14 pmol/punch/hr, GAA activity at 58.3% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 https://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo:

Case13HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.5 mU/U hexosaminid, GAA activity at 17.5% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2482_2646del165 (p.Gly828_Asn882del) (Exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Patient is heterozygous for these variants

Case19HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 8 pmol/spot/hr, GAA activity at 33% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 https://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo:

Case5HPOsFreeText: 10 mg/kg GAA treatment, GAA activity at 0.6 pmol/punch/hr, GAA activity at 6% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Unknown variant, likely a typo

Variant2: NM_000152.4:c.193G>T

ClinVar:

gnomAD:

CaseAddInfo:

Case18HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 2.1 pmol/spot/hr, GAA activity at 35% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.743T>G (p.Leu248Arg)

CAID: CA401363265 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3:c.743T%3EG

gnomAD: Not in gnomAD

CaseAddInfo:

Case16HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.1 umol/h/L, GAA activity at 33% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.722_723delTT (p.Phe241Cysfs*?)

CAID: CA658795235 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.722_723delTT

gnomAD: Not in gnomAD

CaseAddInfo:

Case15HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 8.3 pmol/spot/hr, GAA activity at 35% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2482_2646del165 (p.Gly828_Asn882del) (Exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo:

Case21HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.8 U/g, GAA activity at 8.9% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

No information given to identify where the variant is

Variant2: NM_000152.4: IVS15+2T>A

ClinVar:

gnomAD:

CaseAddInfo:

Case12HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 4 nmol/punch/hr, GAA activity at 15% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.546+1G>T

CAID: CA401361913 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.546%2B1G%3ET

gnomAD: Not in gnomAD

CaseAddInfo:

Patient 12 - LOPD - homozygous

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Case83

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.742delC (p.Leu248Profs*20)

CAID: CA658795236 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.742delC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case57

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1396_1397insG (p.Val466fs*39)

CAID: CA627699396 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1396_1397insG

gnomAD: South Asian 3.271e-5, Overall 4.003e-6 http://gnomad.broadinstitute.org/variant/17-78083807-A-AG

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case89

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.877G>A (p.Gly293Arg)

ClinVar: 4036 https://www.ncbi.nlm.nih.gov/clinvar/variation/4036/

gnomAD: Latino 5.704e-5, Overall 1.807e-5 http://gnomad.broadinstitute.org/variant/17-78081617-G-A

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case66

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1827delC (p.Tyr609*)

ClinVar: 188936 https://www.ncbi.nlm.nih.gov/clinvar/variation/188936/

gnomAD: European (Non-Finnish) 7.181e-5, Overall 3.260e-5 http://gnomad.broadinstitute.org/variant/17-78086448-AC-A

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case68

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1880C>T (p.Ser627Phe)

CAID: CA294896504 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1880C%3ET

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case54

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1437+2T>C

CAID: CA401366685 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1437%2B2T%3EC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Juvenile Late Onset Pompe Disease

Case79

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease, 3 other patients have the same genotype

Case67

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Significance of this variant is unknown.

Variant1: NM_000152.4:c.1835A>C (p.His612Pro)

CAID: CA401369560 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1835A%3EC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case88

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.836G>A (p.Trp279*)

CAID: CA401363637 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.836G%3EA

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case65

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1798C>T (p.Arg600Cys)

CAID: CA8815481 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1798C%3ET

gnomAD: South Asian 3.267e-5, Overall 4.025e-6 http://gnomad.broadinstitute.org/variant/17-78086420-C-T

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case51

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Infantile Onset Pompe Disease

Case77

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.2560C>T (p.Arg854*)

ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case64

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1655T>C (p.Leu552Pro)

ClinVar: 279811 https://www.ncbi.nlm.nih.gov/clinvar/variation/279811/

gnomAD: European (Non-Finnish) 7.053e-5, Overall 3.188e-5 http://gnomad.broadinstitute.org/variant/17-78085800-T-C

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Case60

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1445C>G (p.Pro482Arg)

CAID: CA401366794 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1445C%3EG

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease, 1 person more with the same genotype

Patient6: 47yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0020038

HPOsFreeText: GAA = 7%, BMI = 27.5, normal CT

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk

CaseAddInfo: 14yr disease duration, variants in trans

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient18: 40yo

CasePresentingHPOs: HP:0003325

HPOsFreeText: GAA = 5%, smoker, BMI = 16.3, normal CTA and CT

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 4yr disease duration, variants in trans

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient2: 76yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315, HP:0004887, HP:0000822, HP:0002870, HP:0020038

HPOsFreeText: morning headaches, GAA = 13%, BMI = 23.6, right vertebral artery dominant, nucleo-capsular lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 33yr disease duration

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient9: 54yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315, HP:0004887, HP:0003141, HP:0002870

HPOsFreeText: morning headache, GAA = 7%, smoker, BMI = 23.3, normal CTA, nucleo-capsular and subcortical white matter lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 29yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1551+1G>C

ClinVar: 554983, https://www.ncbi.nlm.nih.gov/clinvar/variation/554983/

gnomAD: n/a

Patient1: 40yo

CasePresentingHPOs:

HPOsFreeText: HyperCKemia, GAA = 4%, BMI = 25.8, normal CTA, temporo-insular lacunes

CaseNotHPOs:

NotHPOsFreeText: no cardiovascular risk factor

CaseAddInfo: 6yr disease duration

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient15: 53yo

CasePresentingHPOs: HP:0002315, HP:0004887, HP:0000822, HP:0003141, HP:0002870, HP:0020038

HPOsFreeText: hyperCKema, morning headaches, GAA = 13%, BMI = 29.6, right ventricular artery dominant, Normal CT

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr disease duration, homozygous variants in trans

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient19: 55yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315, HP:0004887

HPOsFreeText: morning headache, GAA = 6%, BMI = 25, normal CTA, temporo-insular lacunes

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk

CaseAddInfo: 3yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient10: 50yo

CasePresentingHPOs: HP:0003325, HP:0004944, HP:0020038

HPOsFreeText: GAA = 3.6%, BMI = 22.4, MCA M1 4mm aneurysm, normal CT

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk factor

CaseAddInfo: 13yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1551+1G>C

ClinVar: 554983, https://www.ncbi.nlm.nih.gov/clinvar/variation/554983/

gnomAD: n/a

Patient16: 16yo

CasePresentingHPOs: HP:0003325, HP:0020038

HPOsFreeText: GAA = 4.5%, BMI = 21.4, fetal origin of right posterior cerebral artery, normal CT

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk

CaseAddInfo: 6yr disease duration, variants in trans

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient17: 65yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002870, HP:0020038, HP:0002637

HPOsFreeText: GAA = 6.8%, smoker, BMI = 27.1, right ventricular trigone retraction due to ischemia

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 22yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1561G>A (p.Glu521Lys)

ClinVar: 4022, https://www.ncbi.nlm.nih.gov/clinvar/variation/4022/

gnomAD: 8.262e-06, http://exac.broadinstitute.org/variant/17-78084749-G-A

Patient20: 60yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0000822, HP:0002870, HP:0020038

HPOsFreeText: GAA = 11%, BMI = 23.2, subcortical white matter lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1561G>A (p.Glu521Lys)

ClinVar: 4022, https://www.ncbi.nlm.nih.gov/clinvar/variation/4022/

gnomAD: 8.262e-06, http://exac.broadinstitute.org/variant/17-78084749-G-A

Patient11: 62yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0004887, HP:0000822

HPOsFreeText: GAA = 5.7%, smoker, BMI = 22.3, basilar artery fenestration, nucleo-capsular and temporo-insular lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 24yr disease duration, variants in cis

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1551+1G>C

ClinVar: 554983, https://www.ncbi.nlm.nih.gov/clinvar/variation/554983/

gnomAD: n/a

Patient3: 53yo

CasePresentingHPOs: HP:0002870

HPOsFreeText: hyperCKemia, GAA = 16%, BMI = 27.7, left vertebral artery dominant, temporo-insular lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 24yr disease duration

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Case12: Female, 48 years onset, 58 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 59, GAA Activity at ~17 pmol/min/mg before ERT and ~19 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1561G>A (p.Glu521Lys)

ClinVar: 4022 https://www.ncbi.nlm.nih.gov/clinvar/variation/4022/

gnomAD: South Asian 3.266e-5, Overall 3.980e-6 http://gnomad.broadinstitute.org/variant/17-78084749-G-A

CaseAddInfo: Late Onset Pompe Disease

Case4: Female, 40 years onset, 51 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 51, GAA Activity at ~7.5 pmol/min/mg before ERT and ~11 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Case6: Male, 25 years onset, 56 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 57, GAA Activity at ~10.5 pmol/min/mg before ERT and ~11 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1655T>C (p.Leu552Pro)

ClinVar: 279811 https://www.ncbi.nlm.nih.gov/clinvar/variation/279811/

gnomAD: European (Non-Finnish) 7.053e-5, Overall 3.188e-5 http://gnomad.broadinstitute.org/variant/17-78085800-T-C

CaseAddInfo: Late Onset Pompe Disease

Case16: Female, 37 years onset, 49 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 50, GAA Activity at ~4 pmol/min/mg before ERT and ~11 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1465G>A (p.Asp489Asn)

ClinVar: 92465 https://www.ncbi.nlm.nih.gov/clinvar/variation/92465/

gnomAD: European (Finnish) 4.621e-5, Overall 1.195e-5 http://gnomad.broadinstitute.org/variant/17-78084553-G-A

CaseAddInfo: Late Onset Pompe Disease

Case11: Female, 48 years onset, 54 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 54, GAA Activity at ~8.5 pmol/min/mg before ERT and ~9 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Case10: Male, 50 years onset, 52 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 53, GAA Activity at ~13 pmol/min/mg before ERT and ~15 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.784G>A (p.Glu262Lys)

ClinVar: 188806 https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: East Asian 5.016e-5, Overall 1.417e-5 http://gnomad.broadinstitute.org/variant/17-78081447-G-A

CaseAddInfo: Late Onset Pompe Disease

Case5: Male, 65 years onset, 72 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 72, GAA Activity at ~6 pmol/min/mg before ERT and ~10.5 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Case14: Female, 15 years onset, 16 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 16, GAA Activity at ~8 pmol/min/mg before ERT and ~12 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

Case19: Male, 15 years onset, 15.5 years diagnosis, 15 years report

CasePresentingHPOs: HP:0003236 (Increased serum CK)

HPOsFreeText: Asymptomatic hyperCKemia

CaseAddInfo: Late-Onset Pompe Disease

CaseD: Female, 9 months onset, 12 months diagnosis

CasePresentingHPOs: HP:0001270, HP:0003324 (Motor delay, Generalized weakness)

HPOsFreeText: CRIM positive, Requires non-invasive ventilation during nighttime

CaseNotHPOs: HP:0100543, HP:0002540, HP:0001638 (Cognitive impairment, Inability to walk, Cardiomyopathy)

CaseAddInfo: Infantile-Onset Pompe Disease

Case20: Male, 8 years onset, 11 years diagnosis, 11 years report

CasePresentingHPOs: HP:0003236 (Increased serum CK)

HPOsFreeText: Asymptomatic hyperCKemia

CaseAddInfo: Late-Onset Pompe Disease

Case12: Female, Unknown years onset, Unknown years diagnosis, 50 years report

CasePresentingHPOs: HP:0003325, HP:0003327, HP:0003236, HP:0002747 (Limb-girdle muscle weakness, Axial muscle weakness, Increased serum CK, Respiratory muscle weakness)

CaseAddInfo: Late-Onset Pompe Disease

Case#: 5/a, age 29, no age of report

DiseaseAssertion: N/A

FamilyInfo: Family 6, no further information

CasePresenting HPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Family Screening

Variants:

Variant 1: NM_000152.5:c.1921C>G

ClinVar: N/A

CAID: CA401369888

Variant 2:NM_000152.5(GAA):c.-32-13T>G

ClinVar: 4027

ParentalGenotypes: N/A

PreviouslyPublished: N/A

Case#: Subject number 7, male, 50 years (report), 32 years (onset), 38 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0002650, HP:0000360, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (scoliosis, tinnitus, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 4, male, 34 years (report), 5 years (onset), 30 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650 (scoliosis)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0000360, HP:0000365, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (tinnitus, hearing loss, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.258dupC (p.Asn87GlnfsTer9)

Variant 2 ClinVarID: 282842

Variant 2 CAid: CA8814826

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 11, male, 68 years (report), 30s years (onset), 55 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000360 (tinnitus), HP:0002650 (scoliosis), HP:0000939 (osteoporosis), HP:0000821 (hypothyroidism)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walker, cane)

CaseNotHPOs: HP:0000365, HP:0002617, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hearing loss, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1951_1952delGGinsT (p.Gly651SerfsTer?)

Variant 2 ClinVarID: 633225

Variant 2 CAid: CA913191010

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13, male, 50 years (report), 42 years (onset), 45 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

*CasePresentingHPOs:* HP:0000360 (tinnitus), HP:0002650 (scoliosis), HP:0001638 (cardiomyopathy), HP:0001638 (Graves disease), HP:0010788 (testicular cancer), HP:0000821 (hypothyroidism)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0009830, HP:0000939, HP:0000365, HP:0002617 (peripheral neuropathy, osteoporosis, hearing loss, aneurysm)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.525_526delTG (p.Asn177ProfsTer11)

Variant 2 ClinVarID: 189057

Variant 2 CAid: CA274328

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 12, male, 63 years (report), 35 years (onset), 55 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0009830 (peripheral neuropathy)

CaseHPOFreeText: ambulatory, assistive device (cane, wheelchair)

CaseNotHPOs: HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1951_1952delGGinsT (p.Gly651SerfsTer?)

Variant 2 ClinVarID: 633225

Variant 2 CAid: CA913191010

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 10, male, 70 years (report), 58 years (onset), 65 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walking stick occasionally)

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (tinnitus, hypothyroidism, scoliosis, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2655_2656delCG (p.Val886GlufsTer2)

Variant 2 ClinVarID: 597005

Variant 2 CAid: CA913191011

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18, male, 65 years (report), 40 years (onset), 62 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000939 (osteoporosis), HP:0001638 (cardiomyopathy)

CaseHPOFreeText: ambulatory, on BiPAP

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0009830, HP:0100647, HP:0010788 (tinnitus, hypothyroidism, scoliosis, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer)

CaseNotHPOFreeText: no tracheostomy, no infusion reaction

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1051delG

Variant 2 ClinVarID: 188841

Variant 2 CAid: CA274024

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 6, female, 57 years (report), 20s years (onset), 31 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650 (scoliosis)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walker)

CaseNotHPOs: HP:0000360, HP:0000365, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (tinnitus, hearing loss, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 17, female, 33 years (report), 14 years (onset), 24 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000360 (tinnitus)

CaseHPOFreeText: ambulatory

CaseNotHPOs: HP:0009830, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2104C>T

Variant 2 ClinVarID: 189040

Variant 2 CAid: CA274304

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 3, male, 56 years (report), 30s years (onset), 48 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A ** CasePresentingHPOs**: HP:0000365 (hearing loss), HP:0000360 (tinnitus)

CaseHPOFreeText: ambulatory

CaseNotHPOs: HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0002650, HP:0001638 (aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, scoliosis, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2431delC (p.Leu811TrpfsTer?)

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA628018649

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 16, male, 64 years (report), 56 years (onset), 60 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (cane)

CaseNotHPOs: HP:0009830, HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.307T>G

Variant 2 ClinVarID: 92483

Variant 2 CAid: CA220404

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 8, female, 49 years (report), 20s years (onset), 42 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000821 (hypothyroidism)

CaseHPOFreeText: ambulatory, assistive device (quad cane, wheelchair)

CaseNotHPOs: HP:0000365, HP:0002650, HP:0000360, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hearing loss, scoliosis, tinnitus, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1437+2T>C

Variant 2 ClinVarID: 849313

Variant 2 CAid: CA401366685

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 5, male, 59 years (report), 10 years (onset), 33 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000360 (tinnitus), HP:0000939 (osteoporosis)

CaseHPOFreeText: Tracheostomy, assistive device (wheelchair)

CaseNotHPOs: HP:0002650, HP:0002617, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (scoliosis, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no ambulatory, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 15, male, 42 years (report), 15 years (onset), 23 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0009830, HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1134C>G

Variant 2 ClinVarID: 595469

Variant 2 CAid: CA401365023

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9, female, 74 years (report), 30s years (onset), 62 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000360 (tinnitus)

CaseHPOFreeText: Infusion reaction, ambulatory, assistive device (cane for long distance)

CaseNotHPOs: HP:0000821, HP:0002650, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hypothyroidism, scoliosis, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no tracheostomy, not on BiPAP

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2655_2656delCG (p.Val886GlufsTer2)

Variant 2 ClinVarID: 597005

Variant 2 CAid: CA913191011

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Patient6: Female, 53yo

CasePresentingHPOs: HP:0000822, HP:0003077, HP:0001513,

HPOsFreeText: LOPD, smoker

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr follow-up MRI, 17yr disease duration, ERT lasted for 99mo

CasePMIDs: PMID: 25614309

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.1655T>C (p.Leu552Pro)

ClinVar: 279811, https://www.ncbi.nlm.nih.gov/clinvar/variation/279811/

gnomAD: n/a

Patient16: Female, 49yo

CasePresentingHPOs: HP:0003077

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 23yr disease duration, ERT lasted 119mo, 5yr follow-up MRI

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.307T>G (p.Cys103Gly)

ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/

gnomAD: n/a

Patient13: Male, 61yo

CasePresentingHPOs: HP:0003077, HP:0000822

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: homozygous, 13yr disease duration, ERT lasted 29mo

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient7: Male, 59yo

CasePresentingHPOs: HP:0000822, HP:0000819, HP:0003077, HP:0001513

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr follow-up MRI, 14yr disease duration, ERT lasted for 135mo

CasePMIDs: PMID: 25614309

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.307T>G (p.Cys103Gly)

ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/

gnomAD: n/a

Patient1: Female 26yo

CasePresentingHPOs: HP:0003077

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5year follow-up MRI, 15yr disease duration, ERT lasted for 67mo

CasePMIDs: PMID: 25614309

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: IVS9 G > C no ClinVar or CAID

Patient12: Female, 66yo

CasePresentingHPOs: HP:0003077, HP:0000822

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 7yr disease duration, ERT lasted 33mo

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Patient4: Male, 50yo

CasePresentingHPOs: HP:0003077, HP:0005978

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr follow-up MRI, 18yr disease duration, ERT lasted 130mo

CasePMIDs: PMID: 25614309

CasePreviousTesting: same as group

CaseGenotypingMethod: same as grou

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.1495T>A

CAID: CA198789, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA198789

gnomAD: n/a

Patient3: Male, 50yo

CasePresentingHPOs: HP:0003077, HP:0000822

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 5yr follow-up MRI, 40yr disease duration, ERT lasted for 116mo

CasePMIDs: PMID: 25614309

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: c.2136-7delGT no ClinVar, no CAID

Patient18: Male, 49yo

CasePresentingHPOs:

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 13yr disease duration, ERT lasted 84mo

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.3:c.794delG

CAID: CA658795237, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.794delG

gnomAD: n/a

Case2: Male, 46 years onset, 46 years diagnosis, 71 years report, France

CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation)

HPOsFreeText: Lost ambulation at 66 years, Started invasive ventilation at 47 years, Started ERT given every other week at a dose of 20 mg/kg at 66 years for 54 months, Peak Anti-rhGAA antibodies at 1:51,200, FVC at 0.63/16 (L / % expected), MIP at 28 (cm H2O), MEP at 33 (cm H2O), Time off ventilation decreased from 240 to 120 (min/24 h), Total Motor Function Measure from 41 to 44, 6MWT from 20 to 100 meters

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease, Patient died before publication

Case14: Male, 2 years onset, 3 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case11: Female, 9 years onset, 6 years diagnosis (presymptomatic)

CaseAddInfo: Late-Onset Pompe Disease

Case10: Male, 14 years onset, 37 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case13: Male, 9 years onset, 19 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Patient18: female, White British

CasePresentingHPOs: HP:0003677, HP:0003236, HP:0003325, HP:0003701, HP:0003458, HP:0003715, HP:0030231

HPOsFreeText: CK > 10x increase, CK = 599 U/L. Vacuolated, degenerated, and atrophic fibers. Vacuole periphery showed abnormal immunoreactivity for desmin and p62. Z-band streaming of fibers, granular material accumulation. Treated with ERT. Normal to low alpha-glucosidase activity.

CaseNotHPOs: HP:0002093

NotHPOsFreeText: no evidence of glycogenosis

CaseAddInfo: onset after 50yo

CasePreviousTesting: same as group, muscle biopsy, NADH-tetrazolim reductase staining

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Variant2: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient8: Female, Serbian, mid 70s

CasePresentingHPOs: HP:0003325

HPOsFreeText: Normal CK levels

CaseNotHPOs: HP:0003236, HP:0002093

CaseAddInfo: late onset

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.3:c.2051C>G

CAID: CA401370340, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401370340

gnomAD: n/a

Variant2: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Patient32: Male, Caucasian, first investigated at 15yo

CasePresentingHPOs: HP:0003677, HP:0002111, HP:0002875, HP:0003458

HPOsFreeText: CK < 10x increase, CK = 662 U/L. Reduced alpha-glucosidase activity.

CaseNotHPOs: HP:0003325, HP:0002093

CaseAddInfo: onset in childhood, confirmed Pompe Disease via Sanger Sequencing, 2 siblings also carried same variants and presented with reduced enzyme activity but were asymptomatic at time of study.

CasePreviousTesting: same as group, muscle biopsy, EMG

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Variant2: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Case7: Female, 58 years report

HPOsFreeText: 9 years of ERT completed, Forced Vital Capacity at 14%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2041-1G>A

CAID: CA8815596 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.2041-1G%3EA

gnomAD: European (Non-Finnish) 1.012e-5, Overall 4.541e-6 http://gnomad.broadinstitute.org/variant/17-78087016-G-A

CaseAddInfo: Late Onset Pompe Disease

Case6: Male, 65 years report

HPOsFreeText: 8 years of ERT completed, 6 Minute Walking Test at 95 meters, Forced Vital Capacity at 36%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case31: Female, 45 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 457 meters, Forced Vital Capacity at 99%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1636+1G>C

CAID: CA401367398 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1636%2B1G%3EC

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case1: Male, 69 years report

HPOsFreeText: 8 years of ERT completed, 6 Minute Walking Test at 467 meters, Forced Vital Capacity at 61%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.3G>A

CAID: CA401359809 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.3G%3EA

gnomAD: European (Non-Finnish) 8.945e-6, Overall 4.041e-6 http://gnomad.broadinstitute.org/variant/17-78078388-G-A

CaseAddInfo: Late Onset Pompe Disease

Case13: Female, 30 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 520 meters, Forced Vital Capacity at 50%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*42)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Case36: Female, 69 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 252 meters, Forced Vital Capacity at 87%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.854C>G (p.Pro285Arg)

ClinVar: 225114 https://www.ncbi.nlm.nih.gov/clinvar/variation/225114/

gnomAD: European (Non-Finnish) 1.148e-5, Overall 5.109e-6 http://gnomad.broadinstitute.org/variant/17-78081517-C-G

CaseAddInfo: Late Onset Pompe Disease

Case4: Male, 50 years report

HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 140 meters, Forced Vital Capacity at 34%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Late Onset Pompe Disease, Variant is homozygous for this patient

Case28: Female, 49 years report

HPOsFreeText: 6 years of ERT completed, 6 Minute Walking Test at 251 meters, Forced Vital Capacity at 109%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.799_803delinsA (p.Leu267Serfs)

CAID: CA891862613 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.799_803delinsA

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case24: Female, 48 years report

HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 180 meters, Forced Vital Capacity at 67%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case2: Female, 68 years report

HPOsFreeText: 5 years of ERT completed, 6 Minute Walking Test at 275 meters, Forced Vital Capacity at 116%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1629C>G (p.Tyr543Ter)

CAID: CA401367368 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1629C%3EG

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case38: Male, 75 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 246 meters

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1560C>G (p.Asn520Lys)

CAID: CA401367200 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1560C%3EG

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case34: Male, 46 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 383 meters, Forced Vital Capacity at 73%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1888+1G>A

CAID: CA8815511 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1888%2B1G%3EA

gnomAD: European (Non-Finnish) 9.843e-6, Overall 4.375e-6 http://gnomad.broadinstitute.org/variant/17-78086511-G-A

CaseAddInfo: Late Onset Pompe Disease

Case8: Male, 54 years report

HPOsFreeText: 8 years of ERT completed, 6 Minute Walking Test at 300 meters, Forced Vital Capacity at 33%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1888+1G>A

CAID: CA8815511 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1888%2B1G%3EA

gnomAD: European (Non-Finnish) 9.843e-6, Overall 4.375e-6 http://gnomad.broadinstitute.org/variant/17-78086511-G-A

CaseAddInfo: Late Onset Pompe Disease

Case14: Female, 69 years report

HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 200 meters, Forced Vital Capacity at 51%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.118C>T (p.Arg40Ter)

ClinVar: 426593 https://www.ncbi.nlm.nih.gov/clinvar/variation/426593/

gnomAD: South Asian 6.561e-5, Overall 1.428e-5 http://gnomad.broadinstitute.org/variant/17-78078503-C-T

CaseAddInfo: Late Onset Pompe Disease

Case3: Female, 72 years report

HPOsFreeText: 4 years of ERT completed, 6 Minute Walking Test at 264 meters, Forced Vital Capacity at 56%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case5: Male, 57 years report

HPOsFreeText: 2 years of ERT completed, 6 Minute Walking Test at 461 meters, Forced Vital Capacity at 49%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.546+1G>T

CAID: CA401361913 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.546%2B1G%3ET

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case15: Female, 54 years report

HPOsFreeText: 8 years of ERT completed, 6 Minute Walking Test at 229 meters, Forced Vital Capacity at 39%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1717A>C (p.Asn573His)

CAID: CA401369056 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1717A%3EC

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case10: Male, 80 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 220 meters, Forced Vital Capacity at 44%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

Case29: Female, 50 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 354 meters, Forced Vital Capacity at 116%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case37: Female, 62 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 475 meters, Forced Vital Capacity at 94%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case33: Female, 79 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 312 meters, Forced Vital Capacity at 113%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1560C>G (p.Asn520Lys)

CAID: CA401367200 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1560C%3EG

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case16: Female, 61 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 392 meters, Forced Vital Capacity at 52%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.693-1G>C

CAID: CA401362948 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.693-1G%3EC

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case32: Female, 45 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 533 meters, Forced Vital Capacity at 77%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1888+1G>A

CAID: CA8815511 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1888%2B1G%3EA

gnomAD: European (Non-Finnish) 9.843e-6, Overall 4.375e-6 http://gnomad.broadinstitute.org/variant/17-78086511-G-A

CaseAddInfo: Late Onset Pompe Disease

Case19: Male, 57 years report

HPOsFreeText: 8 years of ERT completed, 6 Minute Walking Test at 273 meters, Forced Vital Capacity at 77%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1819_1836del (p.Gly607_His612del )

CAID: CA658795266 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1819_1836del

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease