ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.868C>T (p.Arg290Trp) (rs587778235)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766941 SCV000532701 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DNM2 gene. The R290W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R290W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R290W 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000821354 SCV000962108 uncertain significance Charcot-Marie-Tooth disease, dominant intermediate B 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 290 of the DNM2 protein (p.Arg290Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs587778235, ExAC 0.01%). This variant has not been reported in the literature in individuals with DNM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 133980). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ITMI RCV000120649 SCV000084810 not provided not specified 2013-09-19 no assertion provided reference population

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