Supplementary Data, Table 2
Variant noted to be present in 2 individuals
Variant: NM_000257.3(MYH7):c.2609G>A (p.Arg870His)
ClinVar: 14120, https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
gnomAD: 0.000007072, https://gnomad.broadinstitute.org/variant/14-23894048-C-T
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 one HCM proband
Variant: NM_000257.4(MYH7):c.2609G>A (p.Arg870His)
ClinVarID: 14120 https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
gnomAD: 0.00001549, http://gnomad.broadinstitute.org/variant/14-23894048-C-T
Supplementary Material 4
Case M-26: Japanese
DiseaseAssertion: idiopathic cardiomyopathy (HCM and DCM)
CasePreviousTesting: Clinical evaluation, chest radiography, electrocardiography, echocardiography, cardiac catheterization, full testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1)
CaseGenotypingMethod: 8 sarcomeric genes amplified from genomic DNA via PCR then screened using bidirectional direct sequencing
Variant: NM_000257.3(MYH7):c.2609G>A (p.Arg870His)
ClinVar: 14120, https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
gnomAD: 0.000007072, https://gnomad.broadinstitute.org/variant/14-23894048-C-T
CaseMYH7-17: Australia
DiseaseAssertion: Hypertrophic Cardiomyopathy
FamilyInfo: N/A
CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)
HPOsFreeText: N/A
CaseNotHPOs: N/A
NotHPOsFreeText: N/A
CaseAddInfo: N/A
CasePreviousTesting: See Table 1
CaseGenotypingMethod: DNA was isolated from peripheral blood. Most participants underwent testing from the Illumina Cardiomyopathy Sequencing Panel, which includes 46 cardiomyopathy related genes. For others, whole exome sequencing or Sanger squencing was used. After the results were returned, variants were filtered for pathogenicity and rarity.
Variant: NM_000257.3:c.2609G>A (p.Arg870His)
ClinVar: 14120 https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
gnomAD: European (Non-Finnish) 1.549e-5, Overall 7.072e-6 https://gnomad.broadinstitute.org/variant/14-23894048-C-T
Case#: Consequence 27 Table 1 in Data Supplement (1 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.2609G>A (p.Arg870His)
ClinVar: 14120 https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
CAID: n/a
gnomAD: 0.00001549 European (non-Finnish) https://gnomad.broadinstitute.org/variant/14-23894048-C-T
CaseMYH7-26: N/A
DiseaseAssertion: Hypertrophic Cardiomyopathy
FamilyInfo: N/A
CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)
HPOsFreeText: N/A
CaseNotHPOs: N/A
NotHPOsFreeText: N/A
CaseAddInfo: N/A
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.2609G>A (p.Arg870His)
ClinVar: 14120 https://www.ncbi.nlm.nih.gov/clinvar/variation/14120/
gnomAD: European (Non-Finnish) 1.549e-5, Overall 7.072e-6 https://gnomad.broadinstitute.org/variant/14-23894048-C-T