Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000230399 | SCV000204093 | pathogenic | Hypertrophic cardiomyopathy | 2019-08-29 | criteria provided, single submitter | clinical testing | The p.Gln404X variant in MYBPC3 has been identified in 3 individuals with HCM and segregated with disease from 2 affected relatives from 1 family (LMM data). It was also identified in an individual with early onset DCM who carried an additional loss of funciton variant in MYBPC3 (LMM data). It was absent from large population databases. This nonsense variant leads to a premature termination codon at position 404, which is predicted to lead to a truncated or absent protein. Loss of function of the MYBPC3 gene is an established disease mechanism in autosomal dominant HCM. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HCM. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting. |
Invitae | RCV000230399 | SCV000284204 | pathogenic | Hypertrophic cardiomyopathy | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln404*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy or hypertrophic cardiomyopathy (PMID: 19996403; Invitae). ClinVar contains an entry for this variant (Variation ID: 177796). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000327577 | SCV000329716 | pathogenic | not provided | 2022-08-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27532257, 33087929, 33190526, 25611685, 19996403) |