Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001968435 | SCV002239933 | uncertain significance | Tuberous sclerosis 2 | 2023-08-17 | criteria provided, single submitter | clinical testing | 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: 1462357). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 998 of the TSC2 protein (p.Ala998Thr). 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. |
All of Us Research Program, |
RCV004010995 | SCV004829977 | uncertain significance | Tuberous sclerosis syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004686709 | SCV005181126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-14 | criteria provided, single submitter | clinical testing | The p.A998T variant (also known as c.2992G>A), located in coding exon 26 of the TSC2 gene, results from a G to A substitution at nucleotide position 2992. The alanine at codon 998 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |