Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046628 | SCV001210538 | uncertain significance | Tuberous sclerosis 2 | 2019-01-08 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 1538 of the TSC2 protein (p.Pro1538Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. |
Ambry Genetics | RCV002339236 | SCV002635488 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-17 | criteria provided, single submitter | clinical testing | The p.P1538A variant (also known as c.4612C>G), located in coding exon 35 of the TSC2 gene, results from a C to G substitution at nucleotide position 4612. The proline at codon 1538 is replaced by alanine, an amino acid with highly similar properties. 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. |