Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000550631 | SCV000623620 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-30 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 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 been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 19406073). This variant is also known as IVS6+5G>A. ClinVar contains an entry for this variant (Variation ID: 181049). 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 create or strengthen a 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. |
Ambry Genetics | RCV002399571 | SCV002674526 | uncertain significance | Cardiovascular phenotype | 2019-03-01 | criteria provided, single submitter | clinical testing | The c.772+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 6 in the MYBPC3 gene. This alteration has been reported in a homozygous state in siblings with hypertrophic cardiomyopathy (HCM) whose parents were reported to be consanguineous (Ortiz MF et al. Rev Esp Cardiol, 2009 May;62:572-5). This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |