ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4300G>A (p.Val1434Ile)

gnomAD frequency: 0.00001  dbSNP: rs397516769
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Total submissions: 3
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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 RCV000037501 SCV000061159 uncertain significance not specified 2011-12-23 criteria provided, single submitter clinical testing The Val1434Ile variant (MYH6) has not been previously reported nor previously id entified by our laboratory. Valine (Val) at position 1434 is moderately conserve d in evolutionarily distant species (frog carries a leucine), and this informati on is insufficient to predict if a change would impact the protein. Computationa l predictions on the impact to the protein are mixed (PolyPhen2 = benign, SIFT = pathogenic), though the accuracy of these tools is unknown. Additional informat ion is needed to fully assess the clinical significance of the Val1434Ile varian t.
Invitae RCV001852776 SCV002266667 uncertain significance Hypertrophic cardiomyopathy 14 2021-10-05 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 44508). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs397516769, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 1434 of the MYH6 protein (p.Val1434Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine.
Fulgent Genetics, Fulgent Genetics RCV002482988 SCV002788813 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-20 criteria provided, single submitter clinical testing

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