ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1051G>A (p.Val351Met) (rs876661176)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000218023 SCV000279713 uncertain significance not provided 2016-01-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DNM2 gene. The V351M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. However, the V351M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. 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 a pathogenic variant or a rare benign variant.
Invitae RCV000793937 SCV000933317 uncertain significance Charcot-Marie-Tooth disease, dominant intermediate B 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 351 of the DNM2 protein (p.Val351Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNM2-related disease. ClinVar contains an entry for this variant (Variation ID: 234708). 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.

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