ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5735C>T (p.Ala1912Val)

gnomAD frequency: 0.00004  dbSNP: rs373076710
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
Invitae 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, 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

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