Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001974537 | SCV002213208 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2021-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 614 of the SH3TC2 protein (p.Asp614Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SH3TC2-related conditions. 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. |
| Ambry Genetics | RCV002407122 | SCV002716391 | uncertain significance | Inborn genetic diseases | 2020-12-28 | criteria provided, single submitter | clinical testing | The p.D614Y variant (also known as c.1840G>T), located in coding exon 11 of the SH3TC2 gene, results from a G to T substitution at nucleotide position 1840. The aspartic acid at codon 614 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |