Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000541803 | SCV000644577 | uncertain significance | Tuberous sclerosis 2 | 2017-06-10 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on TSC2 function. The available evidence is currently insufficient to determine its role 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a TSC2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with asparagine at codon 1627 of the TSC2 protein (p.Thr1627Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. |
Ambry Genetics | RCV002330910 | SCV002633862 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.T1627N variant (also known as c.4880C>A), located in coding exon 37 of the TSC2 gene, results from a C to A substitution at nucleotide position 4880. The threonine at codon 1627 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |