Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000557354 | SCV000206034 | likely pathogenic | Hypertrophic cardiomyopathy | 2019-03-07 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
| Invitae | RCV000557354 | SCV000623652 | likely pathogenic | Hypertrophic cardiomyopathy | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 609 of the MYH7 protein (p.Tyr609Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21750094, 27247418, 31737537). ClinVar contains an entry for this variant (Variation ID: 179525). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002408697 | SCV002713138 | likely pathogenic | Cardiovascular phenotype | 2022-06-16 | criteria provided, single submitter | clinical testing | The p.Y609C variant (also known as c.1826A>G), located in coding exon 14 of the MYH7 gene, results from an A to G substitution at nucleotide position 1826. The tyrosine at codon 609 is replaced by cysteine, an amino acid with highly dissimilar 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 reported in several hypertrophic cardiomyopathy (HCM) cases (Waldmüller S et al. Eur J Heart Fail, 2011 Nov;13:1185-92; Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298; Harper AR et al. Nat Genet, 2021 02;53:135-142). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 majority of available evidence to date, this variant is likely to be pathogenic. |