Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000822948 | SCV000963776 | uncertain significance | Tuberous sclerosis 2 | 2024-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 147 of the TSC2 protein (p.Thr147Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TSC2-related conditions and/or tuberous sclerosis (PMID: 35231114, 36030538). ClinVar contains an entry for this variant (Variation ID: 664782). 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 TSC2 protein function. This variant disrupts the p.Thr147 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27859028; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Baylor Genetics | RCV003461281 | SCV004205075 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-06-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004029120 | SCV005036372 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-21 | criteria provided, single submitter | clinical testing | The p.T147A variant (also known as c.439A>G), located in coding exon 4 of the TSC2 gene, results from an A to G substitution at nucleotide position 439. The threonine at codon 147 is replaced by alanine, an amino acid with similar properties. This alteration was detected as mosaic in a Chinese patient with tuberous sclerosis complex (Yang G et al. Clin Genet, 2017 May;91:764-768). 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. |