ClinVar Miner

Submissions for variant NM_000117.2(EMD):c.166G>A (p.Ala56Thr) (rs1057520579)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422963 SCV000516120 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing The A56T variant has not been published as pathogenic or been reported as benign to our knowledge. The A56T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A56T 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. Nevertheless, this substitution occurs at a position that is not conserved. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Lastly, a missense variant in nearby residue has been reported in the Human Gene Mutation Database (Stenson et al., 2014), but the clinical significance of the variant is currently unknown.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign
Invitae RCV000537218 SCV000636281 uncertain significance Emery-Dreifuss muscular dystrophy 1, X-linked 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 56 of the EMD protein (p.Ala56Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EMD-related disease. ClinVar contains an entry for this variant (Variation ID: 379342). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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