Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Biesecker Lab/Clinical Genomics Section, |
RCV000172019 | SCV000054806 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
| Fulgent Genetics, |
RCV000765147 | SCV000896376 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193648 | SCV001362625 | uncertain significance | not specified | 2019-12-24 | criteria provided, single submitter | clinical testing | Variant summary: MYH6 c.5135G>T (p.Ser1712Ile) 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 allele was found at a frequency of 2e-05 in 250274 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5135G>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (MYH7 c.1207C>T, p.Arg403Trp- internal sample), providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001236365 | SCV001409088 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-08-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs201383498, gnomAD 0.005%). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1712 of the MYH6 protein (p.Ser1712Ile). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 191709). |
| Ambry Genetics | RCV002336408 | SCV002642323 | uncertain significance | Cardiovascular phenotype | 2022-03-14 | criteria provided, single submitter | clinical testing | The p.S1712I variant (also known as c.5135G>T), located in coding exon 32 of the MYH6 gene, results from a G to T substitution at nucleotide position 5135. The serine at codon 1712 is replaced by isoleucine, an amino acid with dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |