Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001210156 | SCV001381627 | uncertain significance | Tuberous sclerosis 2 | 2023-08-16 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 940547). 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 glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1654 of the TSC2 protein (p.Gly1654Cys). |
Ambry Genetics | RCV002339539 | SCV002642129 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-06 | criteria provided, single submitter | clinical testing | The p.G1654C variant (also known as c.4960G>T), located in coding exon 37 of the TSC2 gene, results from a G to T substitution at nucleotide position 4960. The glycine at codon 1654 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |