Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236255 | SCV000292859 | likely pathogenic | not provided | 2023-07-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22462672, 32376792) |
| Invitae | RCV001064903 | SCV001229838 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2023-05-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 245766). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1171 amino acid residue in SH3TC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 3000192, 23466821, 25429913). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SH3TC2 protein function. This missense change has been observed in individuals with clinical features of Charcot-Marie-Tooth disease (PMID: 22462672; Invitae). This variant is present in population databases (rs200728983, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1171 of the SH3TC2 protein (p.Arg1171Leu). |
| Molecular Genetics Laboratory, |
RCV000790211 | SCV001335900 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV002450724 | SCV002613076 | uncertain significance | Inborn genetic diseases | 2021-12-21 | criteria provided, single submitter | clinical testing | The p.R1171L variant (also known as c.3512G>T), located in coding exon 16 of the SH3TC2 gene, results from a G to T substitution at nucleotide position 3512. The arginine at codon 1171 is replaced by leucine, an amino acid with dissimilar properties. One patient was reported homozygous for the p.R1171L variant from a cohort of patients with neuropathy and no central nervous system involvement and reduced mean nerve conduction velocity, but detailed clinical information was not provided (Yger M et al. J. Peripher. Nerv. Syst., 2012 Mar;17:112-22). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Inherited Neuropathy Consortium | RCV000790211 | SCV000929603 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
| Genesis Genome Database | RCV000790211 | SCV000999714 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |