Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413523 | SCV000492119 | uncertain significance | not specified | 2016-11-28 | criteria provided, single submitter | clinical testing | The S1148R variant of uncertain significance in the MYBPC3 gene has not been published as a pathogenic or benign variant to our knowledge. This variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or with any significant frequency in the Exome Aggregation Consortium. The S1148R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution also occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, additional evidence is needed to determine whether this variant is pathogenic or benign. |
Invitae | RCV003766163 | SCV004660218 | uncertain significance | Hypertrophic cardiomyopathy | 2023-01-20 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 373521). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs370658083, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1148 of the MYBPC3 protein (p.Ser1148Arg). |