Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158205 | SCV000208140 | pathogenic | not provided | 2017-05-24 | criteria provided, single submitter | clinical testing | Although the c.2995-1 G>A variant has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge, this variant destroys the canonical splice acceptor site in intron 28 and is predicted to cause abnormal gene splicing. The variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the MYBPC3 gene have been reported in association with HCM. In summary, c.2995-1 G>A in the MYBPC3 gene is interpreted as a disease-causing variant |
Mayo Clinic Laboratories, |
RCV000158205 | SCV004226847 | likely pathogenic | not provided | 2023-04-27 | criteria provided, single submitter | clinical testing | PS4_moderate, PVS1 |
Invitae | RCV003586150 | SCV004294788 | pathogenic | Hypertrophic cardiomyopathy | 2023-01-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 180995). Disruption of this splice site has been observed in individuals with hypertrophic cardiomyopathy (PMID: 25132132, 27532257, 33190526). This variant is present in population databases (rs730880584, gnomAD 0.003%). This sequence change affects an acceptor splice site in intron 28 of the MYBPC3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). |