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Table 3 ExAC allele frequencies of the 74 hypertrophic cardiomyopathy “gold standard” missense variants

From: Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation

Gene Variant Effect Classification MAF
MYBPC3 NM_000256.3:c.772G > A p.Glu258Lys Pathogenic 0.0039%a
MYH7 NM_000257.2:c.2389G > A p.Ala797Thr Pathogenic 0.0033%
MYBPC3 NM_000256.3:c.1504C > T p.Arg502Trp Pathogenic 0.0025%
MYH7 NM_000257.2:c.2167C > T p.Arg723Cys Pathogenic 0.0025%
TNNI3 NM_000363.4:c.485G > A p.Arg162Gln Pathogenic 0.0025%
MYH7 NM_000257.2:c.1988G > A p.Arg663His Pathogenic 0.0016%
MYBPC3 NM_000256.3:c.1484G > A p.Arg495Gln Pathogenic 0.00083%
MYL2 NM_000432.3:c.173G > A p.Arg58Gln Pathogenic 0.00083%
MYL2 NM_000432.3:c.64G > A p.Glu22Lys Pathogenic 0.00083%
TNNI3 NM_000363.4:c.433C > T p.Arg145Trp Pathogenic 0.00083%
MYH7 NM_000257.2:c.2609G > A p.Arg870His Pathogenic 0.00082%b
TNNT2 NM_001001430.1:c.274C > T p.Arg92Trp Pathogenic 0.00082%
TNNI3 NM_000363.4:c.433C > G p.Arg145Gly Pathogenic 0.00080%
MYBPC3 NM_000256.3:c.1351G > C p.Glu451Gln Pathogenic 0
MYBPC3 NM_000256.3:c.1505G > A p.Arg502Gln Pathogenic 0
MYBPC3 NM_000256.3:c.2265C > A p.Asn755Lys Pathogenic 0
MYH7 NM_000257.2:c.1207C > T p.Arg403Trp Pathogenic 0
MYH7 NM_000257.2:c.1208G > A p.Arg403Gln Pathogenic 0
MYH7 NM_000257.2:c.1357C > T p.Arg453Cys Pathogenic 0
MYH7 NM_000257.2:c.1750G > C p.Gly584Arg Pathogenic 0
MYH7 NM_000257.2:c.1816G > A p.Val606Met Pathogenic 0
MYH7 NM_000257.2:c.2146G > A p.Gly716Arg Pathogenic 0
MYH7 NM_000257.2:c.2155C > T p.Arg719Trp Pathogenic 0
MYH7 NM_000257.2:c.2156G > A p.Arg719Gln Pathogenic 0
MYH7 NM_000257.2:c.2167C > G p.Arg723Gly Pathogenic 0
MYH7 NM_000257.2:c.2221G > T p.Gly741Trp Pathogenic 0
MYH7 NM_000257.2:c.2717A > G p.Asp906Gly Pathogenic 0
MYH7 NM_000257.2:c.2722C > G p.Leu908Val Pathogenic 0
MYH7 NM_000257.2:c.2770G > A p.Glu924Lys Pathogenic 0
MYH7 NM_000257.2:c.2788G > A p.Glu930Lys Pathogenic 0
MYH7 NM_000257.2:c.4135G > A p.Ala1379Thr Pathogenic 0
MYH7 NM_000257.2:c.438G > T p.Lys146Asn Pathogenic 0
MYH7 NM_000257.2:c.767G > A p.Gly256Glu Pathogenic 0
TNNI3 NM_000363.4:c.470C > T p.Ala157Val Pathogenic 0
TNNI3 NM_000363.4:c.557G > A p.Arg186Gln Pathogenic 0
TNNI3 NM_000363.4:c.575G > A p.Arg192His Pathogenic 0
TNNT2 NM_001001430.1:c.236 T > A p.Ile79Asn Pathogenic 0
TNNT2 NM_001001430.1:c.275G > A p.Arg92Gln Pathogenic 0
TNNT2 NM_001001430.1:c.421C > T p.Arg141Trp Pathogenic 0
TPM1 NM_000366.5:c.523G > A p.Asp175Asn Pathogenic 0
TPM1 NM_000366.5:c.688G > A p.Asp230Asn Pathogenic 0
MYBPC3 NM_000256.3:c.2686G > A p.Val896Met Likely benign 1.28%a
MYBPC3 NM_000256.3:c.833G > A p.Gly278Glu Likely benign 0.29%a
TNNI3 NM_000363.4:c.244C > T p.Pro82Ser Likely benign 0.28%
MYBPC3 NM_000256.3:c.565G > A p.Val189Ile Likely benign 0.27%
MYBPC3 NM_000256.3:c.3413G > A p.Arg1138His Likely benign 0.13%
MYBPC3 NM_000256.3:c.1519G > A p.Gly507Arg Likely benign 0.068%
MYBPC3 NM_000256.3:c.3004C > T p.Arg1002Trp Likely benign 0.067%
TNNI3 NM_000363.4:c.235C > T p.Arg79Cys Likely benign 0.043%
MYBPC3 NM_000256.3:c.1564G > A p.Ala522Thr Likely benign 0.039%
MYBPC3 NM_000256.3:c.440C > T p.Pro147Leu Likely benign 0.038%a
MYH7 NM_000257.2:c.3981C > A p.Asn1327Lys Likely benign 0.010%
MYBPC3 NM_000256.3:c.1147C > G p.Leu383Val Likely benign 0.0089%
MYBPC3 NM_000256.3:c.842G > A p.Arg281Gln Likely benign 0.0070%a
MYBPC3 NM_000256.3:c.1633C > A p.Leu545Met Likely benign 0.0034%
MYBPC3 NM_000256.3:c.1246G > A p.Gly416Ser Likely benign 0.0029%
MYBPC3 NM_000256.3:c.2063C > A p.Thr688Lys Likely benign 0.0019%a
MYBPC3 NM_000256.3:c.3142C > T p.Arg1048Cys Likely benign 0.0017%
TNNT2 NM_001001430.1:c.805A > T p.Asn269Tyr Likely benign 0.0017%a
MYBPC3 NM_000256.3:c.2410C > A p.Leu804Met Likely benign 0
MYH7 NM_000257.2:c.321 T > G p.Asp107Glu Likely benign 0
MYH7 NM_000257.2:c.4555A > T p.Ser1519Cys Likely benign 0
MYH7 NM_000257.2:c.8A > C p.Asp3Ala Likely benign 0
TNNI3 NM_000363.4:c.244C > A p.Pro82Thr Likely benign 0
TNNI3 NM_000363.4:c.253 T > A p.Leu85Met Likely benign 0
TNNI3 NM_000363.4:c.257C > A p.Ala86Asp Likely benign 0
TNNT2 NM_001001430.1:c.682C > G p.Gln228Glu Likely benign 0
MYBPC3 NM_000256.3:c.706A > G p.Ser236Gly Benign 10.79%
MYBPC3 NM_000256.3:c.472G > A p.Val158Met Benign 9.04%a
TNNT2 NM_001001430.1:c.758A > G p.Lys253Arg Benign 5.07%
MYH7 NM_000257.2:c.4472C > G p.Ser1491Cys Benign 0.75%
MYBPC3 NM_000256.3:c.977G > A p.Arg326Gln Benign 0.55%
MYBPC3 NM_000256.3:c.1144C > T p.Arg382Trp Benign 0.42%
MYBPC3 NM_000256.3:c.2498C > T p.Ala833Val Benign 0.22%
  1. Jordan et al. [28] previously published a curated list of 74 “gold standard” missense variants in genes associated with hypertrophic cardiomyopathy. All pathogenic variants were observed at allele frequencies of less than 0.005% in the ExAC dataset
  2. aLoci covered by less than 80,000 total alleles in ExAC
  3. bA variant that did not pass the variant calling quality filter in ExAC