Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158462 | SCV000208397 | pathogenic | not provided | 2017-04-07 | criteria provided, single submitter | clinical testing | The S137X variant in the MYBPC3 gene has been reported in association with HCM in one individual enrolled in a study that analyzed a next-generation sequencing assay for inherited heart diseases; additional clinical information and segregation data was not provided (Wilson et al., 2015). The S137X pathogenic variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the MYBPC3 gene have been reported in HGMD in association with HCM (Stenson et al., 2014). Furthermore, S137X was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, S137X in the MYBPC3 gene is interpreted as a pathogenic variant. |
Invitae | RCV003586153 | SCV004294824 | pathogenic | Hypertrophic cardiomyopathy | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser137*) 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 hypertrophic cardiomyopathy (PMID: 26265630). This variant is also known as p.S137X . ClinVar contains an entry for this variant (Variation ID: 181137). For these reasons, this variant has been classified as Pathogenic. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000158462 | SCV000280270 | pathogenic | not provided | 2011-10-10 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ser137Stop (c.410C>G) in the MYBPC3 gene. This variant has not previously been reported in association with disease and there is no segregation data available. This is a nonsense variant predicted to cause either a truncated protein or complete absence of the protein due to nonsense mediated mRNA decay. Nonsense variants in the MYBPC3 gene are a frequent cause of HCM (p.Gln76Stop, p.Tyr79Stop, p.Gly115Stop, p.Pro161Stop, p.Gln425Stop) as are splicing and frameshift variants (see http://genepath.med.harvard.edu, www.biobaseinternational.com/pages). Based on the predicted functional effect on the resulting protein this variant is likely associated with disease. There is no publicly reported control data on the variant and GeneDx did not report control data. However, it is notable that MYBPC3 nonsense and frameshift variants have not been observed in general population samples. For example, there are no such variants reported in the NHLBI Exome Sequencing Project data set, which currently includes MYBPC3 variant data on over 100 European Americans and over 600 African Americans. Based on these data, it is very likely that this variant predisposes to HCM. |