Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001228269 | SCV001400661 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 452 of the NBN protein (p.Thr452Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NBN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Ambry Genetics | RCV002379872 | SCV002690222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-29 | criteria provided, single submitter | clinical testing | The p.T452I variant (also known as c.1355C>T), located in coding exon 10 of the NBN gene, results from a C to T substitution at nucleotide position 1355. The threonine at codon 452 is replaced by isoleucine, 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. |