ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2783A>C (p.Asp928Ala)

dbSNP: rs727504558
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Total submissions: 2
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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 RCV000155723 SCV000205433 uncertain significance not specified 2013-05-03 criteria provided, single submitter clinical testing The Asp928Ala variant in MYH7 has been reported in 1 individual with HCM as well as 3 asymptomatic relatives (Michels 2009) and was not identified in large popu lation studies (http://evs.gs.washington.edu/EVS/). Another variant at this pos ition (Asp928Asn) has been reported in individuals with HCM (Erdman 2003, Gimeno 2009, Perrot 2005), suggesting that a change at this position may not be tolera ted. Computational analyses (biochemical amino acid properties, conservation, A lignGVGD, PolyPhen2, and SIFT) suggest that the Asp928Ala variant may impact the protein, though this information is not predictive enough to determine pathogen icity. Additional information is needed to fully assess the clinical significan ce of the Asp928Ala variant.
Ambry Genetics RCV002433681 SCV002747283 uncertain significance Cardiovascular phenotype 2017-09-06 criteria provided, single submitter clinical testing The p.D928A variant (also known as c.2783A>C), located in coding exon 21 of the MYH7 gene, results from an A to C substitution at nucleotide position 2783. The aspartic acid at codon 928 is replaced by alanine, an amino acid with dissimilar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Walsh R et al. Genet. Med., 2017 Feb;19:192-203). Other alterations affecting this amino acid (p.D928G, p.D928N, and p.D928V) have been reported in individuals with HCM (Erdmann J et al. Clin Genet. 2003 Oct;64(4):339-49; Michels M. Eur. Heart J. 2009 Nov;30(21):2593-8; Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is highly conserved in available vertebrate species. 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.

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