ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.3511C>T (p.Arg1171Cys) (rs759785462)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517446 SCV000615248 likely pathogenic not provided 2017-03-28 criteria provided, single submitter clinical testing
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000754746 SCV000882636 likely pathogenic Charcot-Marie-Tooth disease, type 4C 2018-10-08 criteria provided, single submitter clinical testing
Invitae RCV000805465 SCV000945422 uncertain significance Charcot-Marie-Tooth disease type 4 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1171 of the SH3TC2 protein (p.Arg1171Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs759785462, ExAC 0.006%). This variant has been observed as homozygous or in combination with another SH3TC2 variant in individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 23466821, 25429913). ClinVar contains an entry for this variant (Variation ID: 448370). 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 observed in affected individuals (PMID: 22462672), which suggests that this may be a clinically significant amino acid residue. 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.
Inherited Neuropathy Consortium RCV000790335 SCV000929745 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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