ClinVar Miner

Submissions for variant NM_000117.2(EMD):c.610C>T (p.Arg204Cys) (rs782299893)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183445 SCV000235905 uncertain significance not provided 2012-12-10 criteria provided, single submitter clinical testing p.Arg204Cys c.610 CGT>TGT in exon 6 of the EMD gene (NM_000117.2): The Arg204Cys variant in the EMD gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Server reports Arg204Cys was not observed in approximately 6,300 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Arg204Cys results in a semi-conservative amino acid substitution of a positively charged Arginine residue with a neutral, polar Cystein residue, which might affect disulfide bonds. In silico analysis predicts Arg204Cys is probably damaging to the protein structure/function. Nevertheless, the Arg204 residue is not well conserved, as a Cysteine residue is present at this position in horse. Also, no missense mutations in nearby codons have been reported in association with EDMD. With the clinical and molecular information available at this time, we cannot definitively determine if Arg204Cys is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s).
Invitae RCV000638225 SCV000759711 uncertain significance Emery-Dreifuss muscular dystrophy 1, X-linked 2018-02-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 204 of the EMD protein (p.Arg204Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs782299893, ExAC 0.006%). This variant has not been reported in the literature in individuals with EMD-related disease. ClinVar contains an entry for this variant (Variation ID: 201776). 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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