Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |