Table 5.
Variants identified in minor HCM genes.
| Patient ID | Genotype | Variant type | AA change | rs ID | CADD | ACMG/ClinVar | GnomAD-AF | Additional variant |
|---|---|---|---|---|---|---|---|---|
| Variants identified in the FLNC gene (transcript NM_001458, MANE select) | ||||||||
| HCM-92 | Het | Missense | Ex4:p.(Ala280Thr) | rs778751919 | 34 | VUS/VUS | 0.00002004 | Unique variant |
| HCM-93 | Het | Missense | Ex13:p.(Asp693Ala) | rs34972246 | 28.9 | VUS/LB | 0.003442 | Unique variant |
| HCM-67 | Het | Missense | Ex23:p.(Arg1341Gln) | rs149641783 | 27.5 | VUS/Conflicting | 0.0009425 | MYH6: p.(Gln277His) |
| HCM-94 | Het | Missense | Ex28:p.(Ala1588Gly) | rs148545460 | 27.5 | VUS/Conflicting | 0.0001603 | Unique variant |
| HCM-95 | Het | Missense | Ex28:p.(Ser1624Leu) | rs879255639 | 34 | VUS/Conflicting | 0.00003189 | Unique variant |
| HCM-66 | Het | Missense | Ex30:p.(Arg1719Cys) | rs773260834 | 34 | VUS/VUS | 0.000008022 | MYH7: p.(Glu1829Lys) |
| HCM-96 | Het | Missense | Ex34:p.(Arg1860Cys) | rs181067717 | 34 | VUS/LB | 0.005209 | Unique variant |
| HCM-97 | Het | Missense | Ex38:p.(Gly2106Val) | NA | 28.6 | NA | NA | Unique variant |
| HCM-98 | Het | Missense | Ex38:p.(Tyr2108Asn) | NA | 28.6 | NA | NA | Unique variant |
| HCM-99 | Het | Missense | Ex40:p.(Gly2199Arg) | rs368977589 | 23.3 | VUS/Conflicting | 0.00003239 | Unique variant |
| HCM-100 | Het | Missense | Ex42:p.(Arg2364His) | rs201672146 | 25.7 | VUS/LB | 0.001724 | MYPN: p.(Pro1112Leu) |
| HCM-101 | Het | Missense | Ex42:p.(Arg2364His) | rs201672146 | 25.7 | VUS/LB | 0.001724 | Unique variant |
| HCM-102 | Het | Missense | Ex47:p.(Lys2637Gln) | rs767794768 | 20.9 | VUS/VUS | 0.00006479 | Unique variant |
| Variants identified in the MYH6 gene (Transcript NM_002471, MANE select) | ||||||||
| HCM-67 | Het | Missense | Ex10:p.(Gln277His) | rs140660481 | 21.9 | VUS/Conflicting | 0.0003677 | FLNC: p.(Arg1341Gln) |
| HCM-68 | Het | Missense | Ex21:p.(Arg860His) | rs115845031 | 24.9 | B /Conflicting | 0.001778 | Unique variant |
| HCM-69 | Het | Missense | Ex22:p.(Glu932Lys) | NA | 34 | VUS/NA | NA | Unique variant |
| HCM-70 | Het | Missense | Ex23:p.(Ala1004Ser) | rs143978652 | 22.9 | LP/Conflicting | 0.0009651 | Unique variant |
| HCM-71 | Het | Missense | Ex28:p.(Glu1295Gln) | rs34935550 | 29.1 | LB/B | 0.003167 | Unique variant |
| HCM-72 | Het | Missense | Ex28:p.(Glu1295Gln) | rs34935550 | 29.1 | LB/B | 0.003167 | Unique variant |
| HCM-40 | Het | Missense | Ex32:p.(Arg1532Leu) | rs34330111 | 34 | VUS/Conflicting | 0.0002794 |
MYBPC3: p.(Ala833Val) SVIL: p.(Thr1630Ser) |
| HCM-52 | Het | Missense | Ex32:p.(His1526Arg) | NA | 25.5 | NA | NA |
MYH7: p.(Asn232Ser) CAV3: p.(Thr78Met) |
| Variants identified in the MYPN gene (transcript NM_032578, MANE select) | ||||||||
| HCM-124 | Het | Missense | Ex2:p.(Gln193Arg) | rs573684358 | 23.0 | LB/VUS | 0.0002188 | Unique variant |
| HCM-100 | Het | Missense | Ex17:p.(Pro1112Leu) | rs71534278 | 27.3 | VUS/VUS | 0.003060 | FLNC: p.(Arg2364His) |
| HCM-125 | Het | Missense | Ex17:p.(Pro1112Leu) | rs71534278 | 27.3 | VUS/VUS | 0.003060 | Unique variant |
| HCM-126 | Het | Missense | Ex17:p.(Pro1112Leu) | rs71534278 | 27.3 | VUS/VUS | 0.003060 | Unique variant |
| HCM-127 | Het | Missense | Ex17:p.(Ala1141Thr) | rs150404143 | 27.7 | B/B | 0.001085 | JPH2: p.(Phe221Leu) |
| HCM-61 | Het | Missense | Ex18:p.(Asp1208Gly) | NA | 29.7 | NA | NA |
MYH7: p.(Arg787Cys) VCL: p.(His636Arg) |
| Variants identified in the ACTN2 gene (transcript NM_001103, MANE select) | ||||||||
| HCM-9 | Het | Missense | Ex10:p.(Thr347Met) | rs727504590 | 33 | B/Conflicting | 0.0001343 | MYBPC3: p.(Arg238Cys) |
| HCM-121 | Het | Missense | Ex12:p.(Arg438Trp) | rs563171274 | 34 | VUS/Conflicting | 0.00001194 | Unique variant |
| HCM-116 | Het | Missense | Ex12:p.(Val458Met) | rs895000018 | 33 | LB/LB | 0.000003985 | TRIM63: p.(Gln247*) |
| HCM-122 | Het | Missense | Ex17:p.(Lys694Asn) | rs748034053 | 24.7 | LB/Conflicting | 0.00003182 | Unique variant |
| HCM-123 | Het | Missense | Ex21:p.(Arg851His) | rs201335965 | 34 | B/Conflicting | 0.00004601 | Unique variant |
| Variants identified in the ALPK3 gene (transcript NM_020778, MANE select) | ||||||||
| HCM-86 | Het | Missense | Ex5:p.(Tyr497Cys) | rs116077141 | 25.6 | B/B | 0.001299 | Unique variant |
| HCM-87 | Het | Missense | Ex7:p.(Arg1483Trp) | rs370816513 | 34 | VUS/VUS | 0.00002784 | Unique variant |
| HCM-88 | Het | Missense | Ex7:p.(Gly1522Asp) | NA | 24.4 | NA | NA | Unique variant |
| HCM-76 | Het | Missense | Ex14:p.(Arg1907Gln) | rs116585466 | 32 | VUS/VUS | 0.0001469 | MYLK2: p.(Gly89Asp) |
| Variants identified in the CSRP3 gene (transcript NM_003476, MANE select) | ||||||||
| HCM-81 | Het | Missense | Ex3:p.(Trp4Arg) | rs45550635 | 26.3 | B/Conflicting | 0.002285 | Unique variant |
| HCM-82 | Het | Missense | Ex3:p.(Trp4Arg) | rs45550635 | 26.3 | B/Conflicting | 0.002285 | SVIL: p.(Thr1630Ser) |
| HCM-83 | Het | Missense | Ex3:p.(Phe30Leu) | NA | 32 | VUS/VUS | NA | Unique variant |
| HCM-84 | Het | Missense | Ex5:p.(Arg100His) | rs138218523 | 24.9 | B/Conflicting | 0.001323 | Unique variant |
| Variants identified in the MYLK2 gene (transcript NM_033118, MANE select) | ||||||||
| HCM-75 | Het | Missense | Ex3:p.(Ala87Thr) | rs753089175 | 22.8 | VUS/VUS | 0.00003595 | Unique variant |
| HCM-76 | Het | Missense | Ex3:p.(Gly89Asp) | rs115398036 | 23 | B/B | 0.004242 | ALPK3: p.(Arg1907Gln) |
| HCM-63 | Het | Missense | Ex11:p.(Ser510Leu) | rs907738836 | 27.9 | NA | NA |
MYH7: p.(Arg869His) TRIM63: p.(Cys75Tyr) |
| Variants identified in the NEXN gene (transcript NM_144573, MANE select) | ||||||||
| HCM-89 | Het | Missense | Ex9:p.(Glu332Ala) | rs201763096 | 23.2 | B/B | 0.004068 | Unique variant |
| HCM-90 | Het | Missense | Ex9:p.(Glu332Ala) | rs201763096 | 23.2 | B/B | 0.004068 | Unique variant |
| Variants identified in the CAV3 gene (transcript NM_033337, MANE select) | ||||||||
| HCM-52 | Het | Missense | Ex2:p.(Thr78Met) | rs72546668 | 23.7 | NA | 0.002667 |
MYH7: p.(Asn232Ser) MYH6: p.(His1526Arg) |
| HCM-91 | Het | Missense | Ex2:p.(Thr78Met) | rs72546668 | 23.7 | NA | 0.002667 | VCL: p.(Arg285Cys) |
| Variants identified in the VCL gene (transcript NM_014000, MANE select) | ||||||||
| HCM-91 | Het | Missense | Ex7:p.(Arg285Cys) | rs757517552 | 34 | VUS/VUS | 0.00001591 | CAV3: p.(Thr78Met) |
| HCM-61 | Het | Missense | Ex14:p.(His636Arg) | rs71579374 | 23.9 | VUS/Conflicting | 0.001485 |
MYH7: p.(Arg787Cys) MYPN: p.(Asp1208Gly) |
| Variants identified in the TCAP gene (transcript NM_003673, MANE select) | ||||||||
| HCM-85 | Het | Missense | Ex2:p.(Met71Thr) | rs143465226 | 23 | VUS/NA | 0.00001669 | Unique variant |
| Variants identified in the JPH2 gene (transcript NM_020433, MANE select) | ||||||||
| HCM-127 | Het | Missense | Ex2:p.(Phe221Leu) | rs558770240 | 23.2 | B/Conflicting | 0.001931 | MYPN: p.(Ala1141Thr) |
AA, amino acid; ACMG, American College of Medical Genetics and Genomics; Het, heterozygous; 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.