Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000223598 | SCV000272167 | uncertain significance | not specified | 2015-08-06 | criteria provided, single submitter | clinical testing | The p.Arg795Gly variant in MYOM1 has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/65584 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s201618512). Computational prediction tools and conservation analysis suggest th at the p.Arg795Gly variant may impact the protein, though this information is no t predictive enough to determine pathogenicity. This variant is located in the l ast three bases of the exon, which is part of the 3' splice region. Computationa l tools do not suggest an impact to splicing. However, this information is not p redictive enough to rule out pathogenicity. In summary, the clinical significan ce of the p.Arg795Gly variant is uncertain. |
| Invitae | RCV001853469 | SCV002273985 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. This variant is present in population databases (rs201618512, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 795 of the MYOM1 protein (p.Arg795Gly). ClinVar contains an entry for this variant (Variation ID: 229019). 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002453772 | SCV002735959 | uncertain significance | Inborn genetic diseases | 2021-11-22 | criteria provided, single submitter | clinical testing | The p.R795G variant (also known as c.2383C>G), located in coding exon 15 of the MYOM1 gene, results from a C to G substitution at nucleotide position 2383. The arginine at codon 795 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |