Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000035927 | SCV000059578 | uncertain significance | not specified | 2014-01-16 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000035927 | SCV001737819 | uncertain significance | not specified | 2021-05-24 | criteria provided, single submitter | clinical testing | Variant summary: MYH7 c.4720C>T (p.Arg1574Trp) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251410 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4720C>T has been reported in the literature in individuals affected with Dilated cardiomyopathy (Pugh_2014, Walsh_2017). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002336117 | SCV002635894 | uncertain significance | Cardiovascular phenotype | 2019-01-14 | criteria provided, single submitter | clinical testing | The p.R1574W variant (also known as c.4720C>T), located in coding exon 32 of the MYH7 gene, results from a C to T substitution at nucleotide position 4720. The arginine at codon 1574 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was reported in two individuals with dilated cardiomyopathy (DCM) (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8: Walsh R et al. Genet. Med., 2017 02;19:192-203). 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. |
| Invitae | RCV003764667 | SCV004682129 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1574 of the MYH7 protein (p.Arg1574Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or left ventricular non-compaction (PMID: 24503780, 27532257, 33500567). ClinVar contains an entry for this variant (Variation ID: 43033). 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 with a positive predictive value of 95%. 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. |