Table 2.

Variants Reported by Panel Testing and WGS That May Cause, or Contribute to, Cardiomyopathy

IDHypertrophic Cardiomyopathy Targeted Test ResultWGS ResultExAC Allele FrequencyReported in Other HCM Probands?
GeneDNA VariantProtein VariantClassificationGeneDNA VariantProtein VariantClassification
1MYBPC3c.2827C>Tp.Arg943XPSame1/16 138 South Asian, 1/64 974 EuropeanY
2MYBPC3c.772G>Ap.Glu258LysPSame3/43 348 EuropeanY
3MYBPC3c.3742_3759dupp.Cys1253_Arg1254insGlyGlyIleTyrValCysPVariant ultimately identified and reported but initially missed by WGSAbsentY
18MYBPC3c.772G>Ap.Glu258LysPSame3/43 348 EuropeanY
19MYBPC3c.2905C>Tp.Gln969XPSameAbsentY
21MYBPC3c.103C>Tp.Arg35TrpVUSSame3/50 036 EuropeanY
27MYBPC3c.927-9G>APSameAbsentY
33MYBPC3c.2747G>Ap.Trp916XPSameAbsentY
35MYBPC3c.3771C>Ap.Asn1257LysVUSSameAbsentY
26MYBPC3c.3005G>Ap.Arg1002GlnVUSVariant identified but did not meet MedSeq WGS reporting standards because of insufficient evidence for pathogenicity4/62 092 EuropeanY
6MYH7c.1987C>Tp.Arg663CysLPSameAbsentY
11MYH7c.4031G>Ap.Arg1344GlnVUSSameAbsentY
ILKc.211delp.Leu71CysfsX26VUSAbsentN
15MYH7c.1357C>Tp.Arg453CysPSameAbsentY
22MYH7c.2717A>Gp.Asp906GlyPSameAbsentY
38MYH7c.2609G>Ap.Arg870HisPSame1/66 732 EuropeanY
34TNNI3c.568G>Tp.Asp190TyrLPSameAbsentY
41MYL2c.484G>Ap.Gly162ArgLPSameAbsentY
31ACTN2c.1839+5G>CVUSSameAbsentN
5ABCC9c.1982G>Ap.Arg661HisVUSSame1/11 498 Latino, 1/66 718 EuropeanN
FLNCc.2450T>Cp.Ile817ThrVUS1/9640 African, 1/16 472 South Asian, 1/65 918 EuropeanN
37ABCC9c.2238-1G>AVUSVariant identified but did not meet MedSeq WGS reporting standards because of insufficient evidence for pathogenicity118/16 384 South Asian, 70/9748 European, 1/9748 AfricanN
4No variant identified*PTPN11c.1403C>Tp.Thr468MetPathogenic1/6614 EuropeanN
  • ABCC9 indicates ATP-binding cassette subfamily C member 9; ACTN2, actinin α2; FLNC, filamin-C; HCM, hypertrophic cardiomyopathy; ILK, integrin-linked kinase; LP, likely pathogenic; MYBPC3, myosin binding protein C; MYH7, cardiac β-myosin heavy chain; MYL2, myosin light chain 2; P, pathogenic; PTPN11, protein tyrosine phosphatase, non-receptor type 11; TNNI3, troponin I; VUS, variant of uncertain significance; and WGS, whole genome sequencing.

  • * Targeted genetic testing panel did not include PTPN11.