ClinVar Miner

Submissions for variant NM_000257.3(MYH7):c.511A>C (p.Asn171His) (rs730880842)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158740 SCV000208675 likely pathogenic not provided 2014-03-09 criteria provided, single submitter clinical testing A N171H variant that is likely pathogenic was identified in the MYH7 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The N171H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N171H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is highly conserved through vertebrates. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (R169G, E170K, T177I, G178R) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in HCM panel(s).
Invitae RCV000706236 SCV000835275 uncertain significance Hypertrophic cardiomyopathy 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 171 of the MYH7 protein (p.Asn171His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 181310). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. 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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