Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048315 | SCV001212313 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2019-12-22 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NBN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 318 of the NBN protein (p.Thr318Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. |
Ambry Genetics | RCV002372803 | SCV002688456 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-07 | criteria provided, single submitter | clinical testing | The p.T318S variant (also known as c.952A>T), located in coding exon 8 of the NBN gene, results from an A to T substitution at nucleotide position 952. The threonine at codon 318 is replaced by serine, 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. |