Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021222 | SCV001182808 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-30 | criteria provided, single submitter | clinical testing | The p.A1273T variant (also known as c.3817G>A), located in coding exon 31 of the TSC2 gene, results from a G to A substitution at nucleotide position 3817. The alanine at codon 1273 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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. |
| Labcorp Genetics |
RCV001226599 | SCV001398920 | uncertain significance | Tuberous sclerosis 2 | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1273 of the TSC2 protein (p.Ala1273Thr). 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: 824256). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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- |
RCV001226599 | SCV002040791 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003117698 | SCV003798680 | uncertain significance | not provided | 2023-01-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown |
| All of Us Research Program, |
RCV004803370 | SCV005427204 | uncertain significance | Tuberous sclerosis syndrome | 2024-09-23 | criteria provided, single submitter | clinical testing |