Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019984 | SCV001181404 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | The p.G111W variant (also known as c.331G>T), located in coding exon 3 of the TSC2 gene, results from a G to T substitution at nucleotide position 331. The glycine at codon 111 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant was identified in 1/190 unrelated Chinese patients under the age of 45 who presented with renal tumors (Wu J et al. Cancer, 2019 04;125:1060-1069). 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 | RCV001242066 | SCV001415128 | uncertain significance | Tuberous sclerosis 2 | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 111 of the TSC2 protein (p.Gly111Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 823605). 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 with a negative predictive value of 95%. 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- |
RCV001242066 | SCV002040537 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ai |
RCV002223258 | SCV002501379 | uncertain significance | not provided | 2021-05-20 | criteria provided, single submitter | clinical testing |