Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000574722 | SCV000675669 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | The p.W167R variant (also known as c.499T>C), located in coding exon 5 of the TSC2 gene, results from a T to C substitution at nucleotide position 499. The tryptophan at codon 167 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in a non-syndromic gastroenteropancreatic neuroendocrine neoplasia patient (Asprino PF et al. Endocr. Relat. Cancer, 2018 Feb;25:L1-L5). This amino acid position is highly 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. |
Invitae | RCV000644193 | SCV000765883 | uncertain significance | Tuberous sclerosis 2 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 167 of the TSC2 protein (p.Trp167Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neuroendocrine neoplasias (PMID: 29167182). ClinVar contains an entry for this variant (Variation ID: 486635). 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. 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. |
Genome- |
RCV000644193 | SCV002040551 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |