ClinVar Miner

Submissions for variant NM_000117.2(EMD):c.608G>A (p.Arg203His) (rs144842093)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183444 SCV000235904 uncertain significance not provided 2017-01-12 criteria provided, single submitter clinical testing The R203H variant of uncertain significance in the EMD gene was reported in a review paper in an individual who developed symptoms of EDMD at 10 years of age; however, a citation for the primary reference about this individual was not provided (Funakoshi et al., 1999). This individual reportedly had a history of muscle weakness and complete atrio-ventricular (AV) conduction block (Funakoshi et al., 1999). Although this variant has not been observed at a significant frequency in large population cohorts, it has been reported as hemizygous in several individuals from these cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server; Exome Aggregation Consortium). The R203H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000551176 SCV000636285 uncertain significance Emery-Dreifuss muscular dystrophy 1, X-linked 2019-02-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 203 of the EMD protein (p.Arg203His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs144842093, ExAC 0.05%) but has not been reported in the literature in individuals with a EMD-related disease. ClinVar contains an entry for this variant (Variation ID: 201775). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.