Submissions for variant NM_024577.3(SH3TC2):c.2671G>A (p.Ala891Thr) (rs779223727)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000206149	SCV000454537	uncertain significance	Charcot-Marie-Tooth disease type 4	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000406192	SCV000454538	uncertain significance	Mononeuropathy of the Median Nerve	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000206149	SCV000259732	uncertain significance	Charcot-Marie-Tooth disease type 4	2015-08-02	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with threonine at codon 891 of the SH3TC2 protein (p.Ala891Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (no rsID, <0.01%) but has not been published in the literature. The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.