Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621567 | SCV000740077 | uncertain significance | Cardiovascular phenotype | 2023-06-17 | criteria provided, single submitter | clinical testing | The p.G1260R variant (also known as c.3778G>C), located in coding exon 33 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 3778. The glycine at codon 1260 is replaced by arginine, an amino acid with dissimilar properties. Another alteration affecting the same amino acid, p.G1260D (c.3779G>A), has been reported in association with dilated cardiomyopathy (DCM) (Hershberger RE et al. Circ Cardiovasc Genet, 2010 Apr;3:155-61). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001860412 | SCV002282266 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-08 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 520320). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1260 of the MYBPC3 protein (p.Gly1260Arg). |