ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4979C>A (p.Ala1660Glu) (rs1006534868)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521554 SCV000617292 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing The A1660E variant has been previously reported in an individual with dilated cardiomyopathy; however, additional detailed clinical information and segregation analysis was not provided (Waldmuller et al., 2011). The A1660E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000688117 SCV000815717 uncertain significance Hypertrophic cardiomyopathy 2018-02-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 1660 of the MYH7 protein (p.Ala1660Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous in an individual affected with dilated cardiomyopathy cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 449317). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be tolerated. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). 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.

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