Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000647050 | SCV000768837 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2021-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 12 of the MYH6 protein (p.Ala12Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs562487638, ExAC 0.01%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 28323875). 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"). 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. |
Ambry Genetics | RCV004985036 | SCV005453698 | uncertain significance | Cardiovascular phenotype | 2024-07-01 | criteria provided, single submitter | clinical testing | The p.A12V variant (also known as c.35C>T), located in coding exon 1 of the MYH6 gene, results from a C to T substitution at nucleotide position 35. The alanine at codon 12 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |