ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.2954A>G (p.Glu985Gly) (rs575937427)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767114 SCV000293644 uncertain significance not provided 2017-10-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SH3TC2 gene. The E985G variant hasnot been published as a pathogenic variant, nor has it been reported as a benign variant to ourknowledge. The E985G variant is observed in 52/30,782 (0.2%) alleles from individuals of South Asian background (Lek et al., 2016). The E985G 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore,based on the currently available information, it is unclear whether this variant is a pathogenic variantor a rare benign variant.
Invitae RCV000477370 SCV000546355 uncertain significance Charcot-Marie-Tooth disease type 4 2019-10-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 985 of the SH3TC2 protein (p.Glu985Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs575937427, ExAC 0.2%). This variant has not been reported in the literature in individuals with SH3TC2-related disease. ClinVar contains an entry for this variant (Variation ID: 246193). 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. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000236841 SCV000605101 uncertain significance not specified 2016-09-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765819 SCV000897212 uncertain significance Charcot-Marie-Tooth disease, type 4C; Mononeuropathy of the median nerve, mild 2018-10-31 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173155 SCV001336232 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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