ClinVar Miner

Submissions for variant NM_024577.4(SH3TC2):c.3512G>A (p.Arg1171His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001225215 SCV001397456 uncertain significance Charcot-Marie-Tooth disease type 4 2019-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1171 of the SH3TC2 protein (p.Arg1171His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200728983, ExAC 0.006%). This variant has not been reported in the literature in individuals with SH3TC2-related conditions. 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 and their clinical significance is uncertain. This variant disrupts the p.Arg1171 amino acid residue in SH3TC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23466821, 25429913, 30001926). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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