Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001235013 | SCV001407677 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-05-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SH3TC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 961334). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SH3TC2 protein function. 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. This variant is present in population databases (rs569256459, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 193 of the SH3TC2 protein (p.Lys193Arg). |
Ambry Genetics | RCV002357010 | SCV002648933 | uncertain significance | Inborn genetic diseases | 2020-11-09 | criteria provided, single submitter | clinical testing | The p.K193R variant (also known as c.578A>G), located in coding exon 6 of the SH3TC2 gene, results from an A to G substitution at nucleotide position 578. The lysine at codon 193 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |