Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154354 | SCV000204017 | pathogenic | Hypertrophic cardiomyopathy | 2013-08-29 | criteria provided, single submitter | clinical testing | The 3331-1G>A variant in MYBPC3 has now been identified by our laboratory in 2 i ndividuals with HCM, including 1 Caucasian individual and 1 individual of unspec ified ancestry. Data from large population studies is insufficient to assess the frequency of this variant. This variant occurs in the invariant region (+/- 1,2 ) of the splice consensus sequence and is predicted to cause altered splicing le ading to an abnormal or absent protein. Truncating variants in MYBPC3 are establ ished as pathogenic for HCM. In summary, this variant meets our criteria to be c lassified as pathogenic (http://pcpgm.partners.org/LMM). |
Invitae | RCV000154354 | SCV001412893 | likely pathogenic | Hypertrophic cardiomyopathy | 2021-09-29 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 177742). Disruption of this splice site has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257, 27600940, 28640247). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 30 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). |
Ambry Genetics | RCV002321634 | SCV002605821 | pathogenic | Cardiovascular phenotype | 2016-05-20 | criteria provided, single submitter | clinical testing | The c.3331-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 31 of the MYBPC3 gene. Since alterations that disrupt the canonical splice acceptor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |