ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.2306A>G (p.Glu769Gly) (rs151317042)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236615 SCV000292762 uncertain significance not provided 2015-04-07 criteria provided, single submitter clinical testing The E769G variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, the E769G 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. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000695202 SCV000823687 uncertain significance Charcot-Marie-Tooth disease type 4 2018-09-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 769 of the SH3TC2 protein (p.Glu769Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs151317042, ExAC 0.09%). This variant has not been reported in the literature in individuals with SH3TC2-related disease. ClinVar contains an entry for this variant (Variation ID: 245704). 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 C35"). 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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