Table 1.
Variants identified in the MYBPC3 gene (transcript NM_000256, MANE select).
| Patient ID | Genotype | Variant type | AA change | rs ID | CADD | ACMG/ClinVar | GnomAD-AF | Additional variant |
|---|---|---|---|---|---|---|---|---|
| HCM-1 | Het | Splicing | Ex4:c.505 + 2 T > A | NA | 23.5 | LP/NA | NA | Unique variant |
| HCM-2 | Het | Stopgain | Ex4:p.(Ser139*) | rs730880704 | 35 | LP/LP | NA | Unique variant |
| HCM-3 | Het | Missense | Ex5:p.(Arg177His) | rs201012766 | 23.5 | B/B | 0.001201 | Unique variant |
| HCM-4 | Het | Stopgain | Ex5:p.(Gln205*) | rs397516061 | 36 | LP/P | NA | Unique variant |
| HCM-5 | Het | Missense | Ex5:p.(Leu183Ile) | NA | 24.3 | VUS/NA | NA | MYBPC3:c.1928-2A > G |
| HCM-6 | Het | Missense | Ex5:p.(Ser217Gly) | rs138753870 | 14.62 | B/Conflicting | 0.001693 | MYBPC3:p.(Arg943*) |
| HCM-7 | Het | Missense | Ex5:p.(Val189Ile) | rs11570052 | 20.0 | B/B | 0.002459 | Unique variant |
| HCM-8 | Het | Missense | Ex5:p.(Val189Ile) | rs11570052 | 20.0 | B/B | 0.002459 | Unique variant |
| HCM-9 | Het | Missense | Ex6:p.(Arg238Cys) | rs771143409 | 33 | VUS/VUS | 0.00001615 | ACTN2: p.(Thr347Met) |
| HCM-10 | Het | Missense | Ex6:p.(Glu258Lys) | rs397516074 | 28.8 | P/P | 0.00002199 | Unique variant |
| HCM-11 | Het | Missense | Ex8:p.(Arg281Gly) | rs371711564 | 23.4 | VUS/VUS | NA | Unique variant |
| HCM-12 | Het | Frameshift deletion | Ex11:p.(Phe305ProfsTer27) | rs397516080 | NA | LP/P | NA | Unique variant |
| HCM-13 | Het | Missense | Ex12:p.(Arg326Gln) | rs34580776 | 24.0 | B/B | 0.004359 | Unique variant |
| HCM-14 | Het | Missense | Ex12:p.(Gly341Ser) | rs397515881 | 34 | VUS/VUS | 0.00004999 | MYBPC3: p.(Pro955ArgfsTer95) |
| HCM-15 | Het | Missense | Ex12:p.(Val321Met) | rs200119454 | 26.5 | VUS/Conflicting | 0.0003297 | Unique variant |
| HCM-16 | Het | Missense | Ex13:p.(Arg382Trp) | rs11570076 | 34 | B/B | 0.004239 | Unique variant |
| HCM-17 | Het | Splicing | Ex14:c.1351 + 2 T > C | rs397515897 | 23.1 | LP/P | NA | Unique variant |
| HCM-18 | Het | Frameshift deletion | Ex14:p.(Val437GlyfsTer13) | rs397515896 | NA | LP/P | NA | Unique variant |
| HCM-19 | Het | Splicing | Ex16:c.1624 + 4A > T | rs397515916 | NA | LP/P | 0.00001334 | Unique variant |
| HCM-20 | Het | Missense | Ex16:p.(Arg495Gln) | rs200411226 | 30 | LP/P | 0.00002408 | Unique variant |
| HCM-21 | Het | Missense | Ex16:p.(Arg495Gln) | rs200411226 | 30 | LP/P | 0.00002408 | Unique variant |
| HCM-22 | Het | Missense | Ex16:p.(Arg495Gly) | rs397515905 | 25.4 | P/P | 0.000004013 | Unique variant |
| HCM-23 | Het | Missense | Ex16:p.(Arg502Trp) | rs375882485 | 34 | P/P | 0.00004632 | Unique variant |
| HCM-24 | Het | Missense | Ex16:p.(Arg502Trp) | rs375882485 | 34 | P/P | 0.00004632 | Unique variant |
| HCM-25 | Het | Missense | Ex16:p.(Arg502Trp) | rs375882485 | 34 | P/P | 0.00004632 | Unique variant |
| HCM-26 | Hom | Missense | Ex17:p.(Ala562Thr) | rs397515919 | 31 | VUS/VUS | NA | Unique variant |
| HCM-27 | Het | Missense | Ex17:p.(Arg597Gln) | rs727503195 | 35 | P/P | 0.00002996 | FHOD3: p.(Arg637Gln) |
| HCM-28 | Het | Missense | Ex18:p.(Glu611Lys) | rs730880555 | 35 | VUS/Conflicting | 0.00002350 | Unique variant |
| HCM-29 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-30 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-31 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-32 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-5 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | MYBPC3: p.(Leu183Ile) |
| HCM-33 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-34 | Het | Splicing | Ex20:c.1928-2A > G | rs397515937 | 23.8 | P/P | NA | Unique variant |
| HCM-35 | Het | Missense | Ex22:p.(Asp770Asn) | rs36211723 | 34 | LP/Conflicting | 0.00001606 | Unique variant |
| HCM-36 | Het | Frameshift insertion | Ex22:p.(Lys754GlufsTer79) | rs774521272 | NA | LP/P | 0.000008025 | Unique variant |
| HCM-37 | Het | Frameshift insertion | Ex22:p.(Lys754GlufsTer79) | rs774521272 | NA | LP/P | 0.000008025 | Unique variant |
| HCM-38 | Het | Frameshift insertion | Ex23:p.(Trp792ValfsTer41) | rs397515963 | NA | P/P | NA | Unique variant |
| HCM-39 | Het | Frameshift insertion | Ex23:p.(Trp792ValfsTer41) | rs397515963 | NA | P/P | NA | SVIL: p.(Ala1496Asp) |
| HCM-40 | Het | Missense | Ex24:p.(Ala833Val) | rs3729952 | 26.9 | B/B | 0.002538 |
MYH6: p.(Arg1532Leu) SVIL: p.(Thr1630Ser) |
| HCM-41 | Het | Missense | Ex24:p.(Arg810His) | rs375675796 | 35 | LP/Conflicting | 0.00004816 | Unique variant |
| HCM-6 | Het | Stopgain | Ex26:p.(Arg943*) | rs387907267 | 43 | P/P | 0.00001214 | MYBPC3: p.(Ser217Gly) |
| HCM-42 | Het | Stopgain | Ex26:p.(Gln969*) | rs397515992 | 38 | LP/P | NA | Unique variant |
| HCM-43 | Het | frameshift deletion | Ex26:p.(Pro955ArgfsTer95) | rs397515990 | NA | P/P | 0.00003187 | Unique variant |
| HCM-14 | Het | frameshift deletion | Ex26:p.(Pro955ArgfsTer95) | rs397515990 | NA | P/P | 0.00003187 | MYBPC3: p.(Gly341Ser) |
| HCM-44 | Het | Missense | Ex28:p.(Arg1022Pro) | rs397516000 | 34 | VUS/Conflicting | 0.00002517 |
MYH7: p.(His1185Gln) TRIM63: p.(Cys23Tyr) |
| HCM-45 | Het | Stopgain | Ex28:p.(Gln1061*) | rs397516005 | 39 | LP/P | 0.00001477 | Unique variant |
| HCM-46 | Het | Missense | Ex30:p.(Arg1138His) | rs187705120 | 35 | VUS/B | 0.001139 | Unique variant |
| HCM-47 | Het | Missense | Ex30:p.(Ile1131Thr) | rs370890951 | 22.5 | B/Conflicting | 0.0008403 | Unique variant |
| HCM-48 | Het | Frameshift deletion | Ex31:p.(Cys1202Leufs*35) | NA | NA | NA | NA | FHOD3: p.(Arg637Gln) |
| HCM-49 | Het | stopgain | Ex32:p.(Cys1244*) | rs730880600 | 38 | LP/P | NA | Unique variant |
| HCM-50 | Het | Stopgain | Ex32:p.(Cys1244*) | rs730880600 | 38 | LP/P | NA | Unique variant |
| HCM-51 | Het | Missense | Ex32:p.(Ser1213Pro) | NA | 25.3 | VUS/NA | NA | Unique variant |
AA, amino acid; ACMG, American College of Medical Genetics and Genomics; Het, heterozygous; Hom, homozygous; B, benign; P, pathogenic; LP, likely pathogenic; VUS, variant of uncertain significance; NA, no data available; Conflicting, conflicting interpretations of pathogenicity; CADD, combined annotation-dependent depletion scores according to CADD model v1.3; GnomAD-AF, allele frequency according to gnomAD V2.1.