Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224703 | SCV001396919 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 413 of the NBN protein (p.Asn413Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002366012 | SCV002666852 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-02 | criteria provided, single submitter | clinical testing | The p.N413D variant (also known as c.1237A>G), located in coding exon 10 of the NBN gene, results from an A to G substitution at nucleotide position 1237. The asparagine at codon 413 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |