CaseIP-2: Male, Taiwan, Birth diagnosis

HPOsFreeText: 4MU enzyme activity at 0.43, MS/MS ennzyme activity at 0.13

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant in literature as c.1396C>T, however the reference has G there. Corrected for poossible typo.

Variant1: NM_000152.4:c.1396G>T (p.Val466Phe)

CAID: CA401366509 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1396G%3ET

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

CaseAddInfo: Infantile Onset Pompe Disease

CaseIP2-11: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.15 umol/hr/L, Serum CK at 662 U/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant2: 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

Variant3: NM_000152.4:c.2303C>T (p.Pro768Leu)

CAID: CA401324900 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.2303C%3ET

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature indicates that Variant 1 and 3 are in trans and that 2 is in cis with one of them

CaseIP2-4: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.08 umol/hr/L, Serum CK at 385 U/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1194+2T>C

ClinVar: 370077 https://www.ncbi.nlm.nih.gov/clinvar/variation/370077/

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant3: 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

CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature indicates Variant 1 and 2 are in trans, also that Variant 3 is in cis with only one of them

CaseOPM-1: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.97 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant2: 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

CaseAddInfo: One Pompe Mutation, Nomenclature indicates Variants 1 and 2 are in cis and the other allele is Wildtype

CaseIP2-6: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.02 umol/hr/L, Serum CK at 709 U/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant2: 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

CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature indicates that Variant 1 and 2 are in cis and the patient is homozygous for this allele, 2 more patients also have the same genotype

Patient7: 6yo

CasePresentingHPOs: HP:0001638

HPOsFreeText: rhGAA dosage = 20 QW, independent walker

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 12days old at ERT start

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.3:c.1062C>G

CAID: CA401364789, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401364789

gnomAD: n/a

Variant3: NM_000152.4(GAA):c.1286A>G (p.Gln429Arg)

ClinVar: 284497, https://www.ncbi.nlm.nih.gov/clinvar/variation/284497/

gnomAD: 0.0007528, http://gnomad.broadinstitute.org/variant/17-78082587-A-G

Patient17: Female, Southern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.4(GAA):c.2815_2816delGT (p.Val939Leufs)

ClinVar: 371481, https://www.ncbi.nlm.nih.gov/clinvar/variation/371481/

gnomAD: 1.653e-05, http://exac.broadinstitute.org/variant/17-78093082-CTG-C

Patient19: Male, Southern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.4(GAA):c.2815_2816delGT (p.Val939Leufs)

ClinVar: 371481, https://www.ncbi.nlm.nih.gov/clinvar/variation/371481/

gnomAD: 1.653e-05, http://exac.broadinstitute.org/variant/17-78093082-CTG-C

Patient11: Male, Southern China

CasePresentingHPOs:

HPOsFreeText: IOPD, survived beyond 2yo, left ventricular mass index and left ventricular posterior wall thickness decreased during ERT. Able to raise head, sit without support, stand, walk alone

CaseNotHPOs: no significant respiratory problems during ERT

NotHPOsFreeText:

CaseAddInfo: homozygous, only patient to receive ERT treatment (rhGAA) every 2wks beginning at 5mo of age. ERT lasted for 90wks.

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Patient4: Female, southern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.4(GAA):c.2185delC (p.Leu729Trpfs) **this is not the same protein transcript listed in paper (p.Thr729fsX8) but I could not find this in clinvar or allele registry)

ClinVar: 370552, https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/

gnomAD: n/a