Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000211805 | SCV000205940 | pathogenic | Hypertrophic cardiomyopathy | 2014-05-08 | criteria provided, single submitter | clinical testing | The Tyr797X variant in MYBPC3 has now been identified by our laboratory in one A sian adult with HCM and one Asian individual with infantile-onset HCM with restr ictive physiology. The infant was homozygous for the Tyr797X variant, which coul d explain the early age of onset. Data from large population studies is insuffic ient to assess the frequency of this variant in the general population. This non sense variant creates a premature stop codon at position 797 thus leading to a t runcated or absent protein. Heterozygous loss of function of the MYBPC3 gene is an established disease mechanism in individuals with HCM. In summary, this varia nt meets our criteria for pathogenicity (http://pcpgm.partners.org/LMM) based on the predicted impact of the variant. |
| Invitae | RCV000211805 | SCV003439733 | pathogenic | Hypertrophic cardiomyopathy | 2022-05-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 179435). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24111713). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr797*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). |