Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001039248 | SCV001202770 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-10-21 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 837827). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs775560235, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1060 of the MYH6 protein (p.Asp1060Asn). |
CHEO Genetics Diagnostic Laboratory, |
RCV001170240 | SCV001332800 | likely benign | Cardiomyopathy | 2017-11-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002320244 | SCV002609281 | uncertain significance | Cardiovascular phenotype | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.D1060N variant (also known as c.3178G>A), located in coding exon 22 of the MYH6 gene, results from a G to A substitution at nucleotide position 3178. The aspartic acid at codon 1060 is replaced by asparagine, an amino acid with highly similar properties. 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. |