Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000214141 | SCV000272029 | uncertain significance | not specified | 2015-07-07 | criteria provided, single submitter | clinical testing | The p.Arg1701Trp variant in MYH6 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/8652 East Asian chromosomes a nd 2/10384 African chromosomes by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org). Computational prediction tools and conservation analy sis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Arg1701Trp variant is uncertain. |
| Ambry Genetics | RCV002347844 | SCV002645810 | uncertain significance | Cardiovascular phenotype | 2022-10-19 | criteria provided, single submitter | clinical testing | The p.R1701W variant (also known as c.5101C>T), located in coding exon 32 of the MYH6 gene, results from a C to T substitution at nucleotide position 5101. The arginine at codon 1701 is replaced by tryptophan, an amino acid with dissimilar properties. This variant co-occurred with an MYBPC3 variant in an individual from a hypertrophic cardiomyopathy cohort (Mademont-Soler I. PLoS One. 2017 Aug;12(8):e0181465). 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 | RCV002517566 | SCV003501454 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-07-01 | 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. 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"). ClinVar contains an entry for this variant (Variation ID: 228896). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs765737102, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1701 of the MYH6 protein (p.Arg1701Trp). |