Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001230933 | SCV001403433 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 399 of the NBN protein (p.Asp399Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 957868). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 | RCV002339633 | SCV002641476 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-26 | criteria provided, single submitter | clinical testing | The p.D399N variant (also known as c.1195G>A), located in coding exon 10 of the NBN gene, results from a G to A substitution at nucleotide position 1195. The aspartic acid at codon 399 is replaced by asparagine, 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. |