Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000206757 | SCV000260917 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2016-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 657 of the SH3TC2 protein (p.Glu657Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs80338925, ExAC <0.01%). This variant was reported in two individuals affected with Charcot-Marie-Tooth disease type 4C, one of whom was homozygous for this variant (PMID: 14574644, 19272779). ClinVar contains an entry for this variant (Variation ID: 21689). Experimental studies have shown that this missense change disrupts SH3TC2 cellular localization, protein-protein interaction, and function (PMID: 20028792). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000020887 | SCV000022747 | pathogenic | Charcot-Marie-Tooth disease, type 4C | 2009-04-01 | no assertion criteria provided | literature only | |
Gene |
RCV000020887 | SCV000041483 | pathologic | Charcot-Marie-Tooth disease, type 4C | 2008-03-31 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Genesis Genome Database | RCV000857147 | SCV000999728 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |