Case#: HCM957, male, 30 years,

DiseaseAssertion: HCM

FamilyInfo: Yes, no other HCM in family

CasePresentingHPOs: syncope (HP:0001279)

CaseHPOFreeText: inverted T-waves, ST-segment depression, left anterior branch block, 28mm MLVWT, 58% LVE F, 1.25 E/A ratio, LVOT-PG 7mm

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: sequencing, physical examination, ECG, 3D modeling, statistical analysis

MultipleGeneVariants:

(1) Variant: NM_000257.4(MYH7):c.2360G>A (p.Arg787His)

ClinVar: 42900 https://www.ncbi.nlm.nih.gov/clinvar/variation/42900/

CAID: N/A

gnomAD: 0.001339 South Asian https://gnomad.broadinstitute.org/variant/14-23894554-C-T

(2) Variant: NM_000257.4(MYH7):c.5561C>T (p.Thr1854Met)

ClinVar: 161320 https://www.ncbi.nlm.nih.gov/clinvar/variation/161320/

CAID: N/A

gnomAD: 0.00005423 European (Non-Finnish) https://gnomad.broadinstitute.org/variant/14-23883310-G-A

Case#: HCM275, male, 59 years, I-1

DiseaseAssertion: HCM

FamilyInfo: Yes, daughter has HCM

CasePresentingHPOs: syncope (HP:0001279)

CaseHPOFreeText: inverted T-waves, ST-segment depression, 28mm MLVWT, 65% LVE F, 1.3 E/A ratio, LVOT-PG 68mm

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: sequencing, physical examination, ECG, 3D modeling, statistical analysis

MultipleGeneVariants:

(1) Variant: NM_000257.4(MYH7):c.2081G>A (p.Arg694His)

ClinVar: 264068 https://www.ncbi.nlm.nih.gov/clinvar/variation/264068/

CAID: N/A

gnomAD: 0.00004008 African/African-American https://gnomad.broadinstitute.org/variant/14-23895254-C-T

(2) Variant: NM_000257.4(MYH7):c.4985G>A (p.Arg1662His)

ClinVar: 43049 https://www.ncbi.nlm.nih.gov/clinvar/variation/43049/

CAID: N/A

gnomAD: 0.0002894 Ashkenazi Jewish https://gnomad.broadinstitute.org/variant/14-23885010-C-T

Case#: II-9, female, 46 yrs

DiseaseAssertion: HCM

FamilyInfo: Yes, 2 siblings and niece have HCM

CasePresentingHPOs: chest tightness, palpitations (HP:0031352, HP:0001962)

CaseHPOFreeText: T flattened and inverted and left axis deviation (-48 degrees), 22mm MLVWT, 63% LVE F, 1.29 E/A ratio, LVOT-PG 4mm

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: sequencing, physical examination, ECG, 3D modeling, statistical analysis

MultipleGeneVariants:

(1) Variant: absent (MYH7- A934V)

ClinVar: N/A

CAID: CA389047003

gnomAD: absent

(2) Variant: NM_000257.4(MYH7):c.4159G>A (p.Glu1387Lys)

ClinVar: 181244 https://www.ncbi.nlm.nih.gov/clinvar/variation/181244/

CAID: N/A

gnomAD: 0.00003266 South Asian https://gnomad.broadinstitute.org/variant/14-23887429-C-T

Case#: KMP 1, female, 39 yrs, East Slovakia

DiseaseAssertion: HCM

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: symptomatic; LVEF 60%; NYHA I.; ECG; echocardiography

CaseNotHPOs: n/a

CaseNotHPOFreeText: no LVOTO; no ICD

CasePreviousTesting: Additional Sanger sequencing of exons 12, 24, 25 of MYBPC3, exon 12 NEBL, exons 12, 20, 21 of SCN5A, exon 7 of TNNI3, and exon 9 of TNNT2 gene

CaseGenotypingMethod: Sanger sequencing

Variant: NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)

ClinVar: 14093 https://www.ncbi.nlm.nih.gov/clinvar/variation/14093/

CAID: n/a

gnomAD: absent

Case#: KMP 16, female, 60 yrs, East Slovakia

DiseaseAssertion: HCM

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: symptomatic; LVOTO yes; LVEF 39-40%; NYHA I.; ICD yes; ECG; echocardiography;

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: Additional Sanger sequencing of exons 12, 24, 25 of MYBPC3, exon 12 NEBL, exons 12, 20, 21 of SCN5A, exon 7 of TNNI3, and exon 9 of TNNT2 gene

CaseGenotypingMethod: Sanger sequencing;

Variant: NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)

ClinVar: 14093 https://www.ncbi.nlm.nih.gov/clinvar/variation/14093/

CAID: n/a

gnomAD: absent

Case#: KMP 1, female, 39 yrs, East Slovakia

DiseaseAssertion: HCM

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: symptomatic; LVEF 60%; NYHA I.; ECG; echocardiography

CaseNotHPOs: n/a

CaseNotHPOFreeText: no LVOTO; no ICD

CasePreviousTesting: Additional Sanger sequencing of exons 12, 24, 25 of MYBPC3, exon 12 NEBL, exons 12, 20, 21 of SCN5A, exon 7 of TNNI3, and exon 9 of TNNT2 gene

CaseGenotypingMethod: Sanger sequencing

Variant: NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)

ClinVar: 14093 https://www.ncbi.nlm.nih.gov/clinvar/variation/14093/

CAID: n/a

gnomAD: absent

Case#: KMP 16, female, 60 yrs, East Slovakia

DiseaseAssertion: HCM

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: symptomatic; LVOTO yes; LVEF 39-40%; NYHA I.; ICD yes; ECG; echocardiography;

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: Additional Sanger sequencing of exons 12, 24, 25 of MYBPC3, exon 12 NEBL, exons 12, 20, 21 of SCN5A, exon 7 of TNNI3, and exon 9 of TNNT2 gene

CaseGenotypingMethod: Sanger sequencing;

Variant: NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)

ClinVar: 14093 https://www.ncbi.nlm.nih.gov/clinvar/variation/14093/

CAID: n/a

gnomAD: absent

PatientID: 1

KindredID: 1

Case: F, 40Y0M, Caucasian

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0006880, HP:0006770, HP:0006748, HP:0001737, HP:0000107, HP:0009713 (Cerebellar hemangioblastoma, Clear cell renal cell carcinoma, Adrenal pheochromocytoma, Pancreatic cysts, Renal cyst, Spinal hemangioblastoma)

CaseHPOFreeText: The patient was found to have two extraneuraxial hemangioblastomas, the locations of these tumors included intra/paraspinal (extradural) and the nerve roots. Her past medical history included  cerebellar hemangioblastomas, clear cell renal cell carcinoma, an adrenal pheochromocytoma, and cysts in both the   kidney and  pancreas. Clinical symptoms and imaging features include Radicular lumbarpain, lowerlimb paresthesia &weakness/CT, MRI: contrastenhancing masses &erosion of lumbarspine & sacrum.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal kidney.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplemental Digital Content 1. Primer Sequences for VHL gene amplification, LOH and methylation analysis.

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: CA020454 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.500G%3EA

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500G>A) and I151N (c.452T>A)

MultipleGeneVariants: Germline, VHL, c. 452T>A (p.Ile151Asn)

PatientID: 1

KindredID: 1

Case: F, 40Y0M, Caucasian

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0006880, HP:0006770, HP:0006748, HP:0001737, HP:0000107, HP:0009713 (Cerebellar hemangioblastoma, Clear cell renal cell carcinoma, Adrenal pheochromocytoma, Pancreatic cysts, Renal cyst, Spinal hemangioblastoma)

CaseHPOFreeText: The patient was found to have two extraneuraxial hemangioblastomas, the locations of these tumors included intra/paraspinal (extradural) and the nerve roots. Her past medical history included  cerebellar hemangioblastomas, clear cell renal cell carcinoma, an adrenal pheochromocytoma, and cysts in both the   kidney and  pancreas. Clinical symptoms and imaging features include Radicular lumbarpain, lowerlimb paresthesia &weakness/CT, MRI: contrastenhancing masses &erosion of lumbarspine & sacrum.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal kidney.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplemental Digital Content 1. Primer Sequences for VHL gene amplification, LOH and methylation analysis.

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: CA020454 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.500G%3EA

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500G>A) and I151N (c.452T>A)

MultipleGeneVariants: Germline, VHL, c. 452T>A (p.Ile151Asn)