Table 2.
Cases/Controls with pathogenic/likely pathogenic variants and VUS+ in cardiomyopathy genes with AD pattern of inheritance.
| Age | Sex, race | Phenotype criteria | Gene | Type | Variant | Transcript | ClinVar interpretation | ACMG interpretation | gnomAD AF in ethnic group | Associated disease | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases | |||||||||||
| C1 | 50–60 | F, African | High ECV | SCN5A | Missense | 3:38613773G>A | p.Arg225Trp | P/LP | Pathogenic | 1.28e−4 | DCM, LVNC |
| C2 | 70–80 | F, African | High Native T1 | CRYAB | Missense | 11:111908822G>A | p.Arg157His | VUS | Likely pathogenic | 6.15e−5 | DCM, LVNC |
| High ECV | |||||||||||
| C3 | 50–60 | M, Chinese | High Native T1 | CRYAB | Start codon loss | 11:111911722G>A | p.Met1Ile | Conflicting | Likely pathogenic | 9.84e−4 | DCM, LVNC |
| C4 | 80–90 | F, White | High Native T1 | MYH7 | Missense | 14:23424839G>A | p.Arg870His | Pathogenic | Likely pathogenic | 1.55e−5 | HCM, DCM, LVNC |
| High ECV | |||||||||||
| C5 | 60–70 | M, African | High Native T1 | MYH7 | Missense | 14:23429037C>T | p.Arg442His | Conflicting | Likely pathogenic | 6.15e−5 | HCM, DCM, LVNC |
| C6 | 50–60 | M, Hispanic | High ECV | MYBPC3 | Missense | 11:47337543G>A | p.Arg817Gln | Conflicting | VUS+ | 2.83e−5 | HCM, DCM, LVNC |
| C7 | 70–80 | M, White | High Native T1 | MYBPC3 | Missense | 11:47337792G>A | p.Val771Met | Conflicting | VUS+ | 1.76e−5 | HCM, DCM, LVNC |
| High ECV | |||||||||||
| Controls | |||||||||||
| N1 | 50–60 | M, Hispanic | – | MYL2 | Missense | 12:110914290C>T | p.Gly57Glu | VUS | Likely pathogenic | 2.89e−5 | HCM |
| N2 | 60–70 | M, White | – | TNNT2 | Missense | 1:201365261G>A | p.Ala114Val | Conflicting | VUS+ | 1.76e−5 | HCM, DCM, RCM, LVNC |
*VUS+: Variants that were VUS without adjustment of ACMG/AMP criteria.
ECV, Extracellular volume; DCM, Dilated cardiomyopathy; LVNC, Left ventricular non-compaction; HCM, Hypertrophic cardiomyopathy; RCM, Restrictive cardiomyopathy.