DiseaseAssertion: Hypertrophic Cardiomyopathy

VariantPreviousTesting: ACTC1, ACTN2, CSRP3, LAMP2, MYBPC3, MYH7, NEXN, PLN, TNNC1, TNNI3, TNNT2, TPM1, CAV3, GLA, MYL2, MYL3, MYOZ2, PRKAG2, and TTR were all tested via NGS.

VariantGenotypingMethod: Next-generation sequencing panels were used to sequence and read the genetic information of the 760 HCM probands for variants within exons and in +/- 10 nucleotides within the flanking introns of the genes provided above. These variants were then interpreted and filtered for pathogenicity.

VariantAddInfo: Seen in five HCM probands and one PanCM proband

Variant: NM_000257.4(MYH7):c.1750G>C (p.Gly584Arg)

ClinVarID: 14090 https://www.ncbi.nlm.nih.gov/clinvar/variation/14090/

gnomAD: 0.000008790, http://gnomad.broadinstitute.org/variant/14-23896932-C-G

CaseMYH7-17: N/A

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

HPOsFreeText: N/A

CaseNotHPOs: N/A

NotHPOsFreeText: N/A

CaseAddInfo: 3 other probands share this genotype

CaseGenotypingMethod: Testing for all 8 sarcomeric genes, plus GLA, LAMP2, and PRKAG2 was initiated in all probands. After the direct sequencing, the variants were filtered for pathogenicity and classified.

Variant: NM_000257.3:c.1750G>C (p.Gly584Arg)

ClinVar: 14090 https://www.ncbi.nlm.nih.gov/clinvar/variation/14090/

gnomAD: European (Non-Finnish) 8.790e-6, Overall 3.976e-6 https://gnomad.broadinstitute.org/variant/14-23896932-C-G

Case#: Consequence 18 Table 1 in Data Supplement (4 cases)

DiseaseAssertion: HCM

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Cardiac magnetic resonance imaging, BSA, NYHA functional class, obstructive HCM, atrial fibrillation, coronary artery disease, NSVT, Syncope, SCD family hitory, wall thickness

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Additional oligonucleotide hybridization–based DNA sequencing and dideoxy-based DNA sequencing for MYBPC3, TMP1, TNNC1, TNNI2, TNNI3, TNNT2, ACTC1, MYL3

CaseGenotypingMethod: oligonucleotide hybridization–based DNA sequencing and dideoxy-based DNA sequencing

Variant: NM_000257.4(MYH7):c.1750G>C (p.Gly584Arg)

ClinVar: 14090 https://www.ncbi.nlm.nih.gov/clinvar/variation/14090/

CAID: n/a

gnomAD: 0.000008790 European (non-Finnish) https://gnomad.broadinstitute.org/variant/14-23896932-C-G