Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Diagnostics Laboratory, |
RCV001730486 | SCV001981532 | likely pathogenic | Tuberous sclerosis 2 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002381358 | SCV002692117 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-04 | criteria provided, single submitter | clinical testing | The p.V334A variant (also known as c.1001T>C), located in coding exon 10 of the TSC2 gene, results from a T to C substitution at nucleotide position 1001. The valine at codon 334 is replaced by alanine, an amino acid with similar properties. Analysis of this alteration in a transfection-based immunoblot assay showed impaired function compare to wild type TSC2 (Hoogeveen-Westerveld M et al. Hum Mutat, 2011 Apr;32:424-35). This variant was reported in a cohort of patients with an autism spectrum disorder (Bahl S et al. Mol Autism, 2013 Mar;4:5). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001730486 | SCV003443059 | uncertain significance | Tuberous sclerosis 2 | 2022-05-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies have shown that this missense change affects TSC2 function (PMID: 21309039). 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 TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 65217). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 334 of the TSC2 protein (p.Val334Ala). |
| Tuberous sclerosis database |
RCV000055437 | SCV000083658 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |