Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155801 | SCV000205512 | uncertain significance | not specified | 2014-07-03 | criteria provided, single submitter | clinical testing | The Ala1912Val variant in MYH6 has not been previously reported in individuals w ith cardiomyopathy or in large population studies, but has been identified in 1/ 4406 African American chromosomes by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs373076710). Computational prediction tools a nd conservation analysis suggest that this variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. In summa ry, the clinical significance of the Ala1912Val variant is uncertain. |
| Labcorp Genetics |
RCV001351716 | SCV001546210 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-09-21 | 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: 179021). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs373076710, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1912 of the MYH6 protein (p.Ala1912Val). |
| Ambry Genetics | RCV002345508 | SCV002650668 | uncertain significance | Cardiovascular phenotype | 2021-06-22 | criteria provided, single submitter | clinical testing | The p.A1912V variant (also known as c.5735C>T), located in coding exon 36 of the MYH6 gene, results from a C to T substitution at nucleotide position 5735. The alanine at codon 1912 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Fulgent Genetics, |
RCV002492589 | SCV002800921 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-10-14 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004734737 | SCV005353661 | uncertain significance | MYH6-related disorder | 2024-09-13 | no assertion criteria provided | clinical testing | The MYH6 c.5735C>T variant is predicted to result in the amino acid substitution p.Ala1912Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |