Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172018 | SCV000050988 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002345586 | SCV002646634 | uncertain significance | Cardiovascular phenotype | 2024-10-17 | criteria provided, single submitter | clinical testing | The p.R1714W variant (also known as c.5140C>T), located in coding exon 32 of the MYH6 gene, results from a C to T substitution at nucleotide position 5140. The arginine at codon 1714 is replaced by tryptophan, an amino acid with dissimilar properties. 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 variant remains unclear. |
Labcorp Genetics |
RCV003629103 | SCV004517632 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-10-21 | 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 1714 of the MYH6 protein (p.Arg1714Trp). This variant is present in population databases (rs140651265, gnomAD 0.009%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32880476). ClinVar contains an entry for this variant (Variation ID: 191708). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH6 protein function with a positive predictive value of 80%. 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. |