Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000999579 | SCV001156280 | likely pathogenic | Hypertrophic cardiomyopathy | 2018-10-16 | criteria provided, single submitter | research | The MYBPC c.2738-2A>T variant is not observed in large population databases such as the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We have identified this variant in one proband with HCM (Ingles J, et al., 2017). This variant affects the canonical splice acceptor site of intron 26, and is therefore predicted to cause abnormal splicing. Interestingly, other rare variants at this position (c.2738-2A>C; c.2738-2A>G) have been reported in HCM patients (Zou Y, et al., 2013; Walsh R, et al., 2017), suggesting that single nucleotide changes at this position may not be tolerated. Loss of function variants in MYBPC3 are a known mechanism of disease in HCM and splice variants in MYBPC3 have been shown to be disease-causing. Hence, we classify MYBPC3 c.2738-2A>T as "likely pathogenic". |