Submissions for variant NM_024577.3(SH3TC2):c.3847G>T (p.Gly1283Cys) (rs370844006)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000812065	SCV000952367	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-12-24	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with cysteine at codon 1283 of the SH3TC2 protein (p.Gly1283Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs370844006, ExAC 0.003%). 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. 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.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000998459	SCV001154545	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173829	SCV001336945	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing