ClinVar Miner

Submissions for variant NM_016156.5(MTMR2):c.14C>G (p.Ser5Trp) (rs778430688)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000431441 SCV000534764 uncertain significance not provided 2016-12-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MTMR2 gene. The S5W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S5W variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S5W 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. However, 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 RCV000167965 SCV000218613 uncertain significance Charcot-Marie-Tooth disease type 4 2018-02-26 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 5 of the MTMR2 protein (p.Ser5Trp). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MTMR2-related disease. ClinVar contains an entry for this variant (Variation ID: 188111). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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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