Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024291 | SCV001186276 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-05 | criteria provided, single submitter | clinical testing | The p.S186T variant (also known as c.556T>A), located in coding exon 5 of the NBN gene, results from a T to A substitution at nucleotide position 556. The serine at codon 186 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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. |
| Invitae | RCV001862284 | SCV002147913 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 186 of the NBN protein (p.Ser186Thr). 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: 825838). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine 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. |