ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1684A>G (p.Asn562Asp)

gnomAD frequency: 0.00001  dbSNP: rs397516118
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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 RCV000035738 SCV000059389 uncertain significance not specified 2013-01-23 criteria provided, single submitter clinical testing The Asn562Asp variant in MYH7 has not been reported in the literature nor previo usly identified by our laboratory. This variant has also not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS), which increases the likelihood that the variant is pathogenic. However, we cannot exclude that it m ay be common in other populations. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. Additional information is nee ded to fully assess the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health RCV001183467 SCV001349206 uncertain significance Cardiomyopathy 2023-10-12 criteria provided, single submitter clinical testing This missense variant replaces asparagine with aspartic acid at codon 562 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003586135 SCV004281172 uncertain significance Hypertrophic cardiomyopathy 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 562 of the MYH7 protein (p.Asn562Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 42857). 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 expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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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