Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001225862 | SCV001398156 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 953554). 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 is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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 C15"). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25132132, 31737537). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 878 of the MYH7 protein (p.Val878Met). |
| Ambry Genetics | RCV002429958 | SCV002741251 | uncertain significance | Cardiovascular phenotype | 2022-07-25 | criteria provided, single submitter | clinical testing | The p.V878M variant (also known as c.2632G>A), located in coding exon 20 of the MYH7 gene, results from a G to A substitution at nucleotide position 2632. The valine at codon 878 is replaced by methionine, an amino acid with highly similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This variant has been detected in an individual from a hypertrophic cardiomyopathy (HCM) cohort and a cohort referred for HCM genetic testing (Wang J et al. Eur J Heart Fail, 2014 Sep;16:950-7; Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |