Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037543 | SCV000061201 | uncertain significance | not specified | 2012-08-20 | criteria provided, single submitter | clinical testing | The Asp310Asn variant in MYH6 has not been reported in the literature but has be en identified in 1/4406 African American chromosomes and 1/8600 European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS/). These could represent presymptomatic individual s. Computational analyses (biochemical amino acid properties, conservation, Alig nGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impa ct to the protein. Additional information is needed to fully assess the clinical significance of the Asp310Asn variant. |
| Invitae | RCV001852779 | SCV002276538 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 310 of the MYH6 protein (p.Asp310Asn). This variant is present in population databases (rs374692396, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 44547). 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 not expected to disrupt MYH6 protein function with a negative 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. |
| Ai |
RCV002223770 | SCV002501817 | uncertain significance | not provided | 2022-02-17 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002482991 | SCV002782028 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-08-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003162325 | SCV003906429 | uncertain significance | Cardiovascular phenotype | 2023-01-17 | criteria provided, single submitter | clinical testing | The p.D310N variant (also known as c.928G>A), located in coding exon 9 of the MYH6 gene, results from a G to A substitution at nucleotide position 928. The aspartic acid at codon 310 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in a pediatric cardiomyopathy cohort; however, clinical details were limited and additional alterations in other cardiac-related genes were identified (Burstein DS et al. Pediatr Res, 2021 May;89:1470-1476). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |