Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486610 | SCV000567281 | pathogenic | not provided | 2015-07-10 | criteria provided, single submitter | clinical testing | Although the c.3191-3 C>G variant has not been reported as a pathogenic variant or as a benignpolymorphism to our knowledge, this variant is predicted to destroy the splice acceptor site in intron 29and cause abnormal gene splicing. The variant is predicted to lead to either an abnormal message that issubject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used forprotein translation. Other splice site variants in the MYBPC3 gene have been reported in HGMD inassociation with HCM (Stenson P et al., 2014). Furthermore, the c.3191-3 C>G variant was not observedin approximately 6100 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. Therefore, we consider the c.3191-3 C>G variant to be pathogenic. |
Invitae | RCV001321874 | SCV001512725 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 29 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 419467). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |