Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV002285271 | SCV000208724 | pathogenic | not provided | 2022-09-20 | criteria provided, single submitter | clinical testing | Identified in patient with MYH7-related disorders in published literature (Van Driest et al., 2004; Mattivi et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15358028, 26659599, 27532257, 29300372, 33065066, 32894683) |
| Labcorp Genetics |
RCV001054191 | SCV001218494 | uncertain significance | Hypertrophic cardiomyopathy | 2021-06-19 | 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. This variant disrupts the p.Val404 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been observed in individuals with MYH7-related conditions (PMID: 12975413), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 15358028). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 404 of the MYH7 protein (p.Val404Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| Ambry Genetics | RCV004649078 | SCV005143057 | uncertain significance | Cardiovascular phenotype | 2024-03-24 | criteria provided, single submitter | clinical testing | The p.V404M variant (also known as c.1210G>A), located in coding exon 11 of the MYH7 gene, results from a G to A substitution at nucleotide position 1210. The valine at codon 404 is replaced by methionine, an amino acid with highly similar properties. This alteration has been reported in a subject with hypertrophic cardiomyopathy (HCM) (Van Driest SL et al. J Am Coll Cardiol, 2004 Aug;44:602-10). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |