Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001067335 | SCV001232390 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with serine at codon 197 of the NBN protein (p.Tyr197Ser). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and serine. 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 | RCV002355090 | SCV002652591 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-24 | criteria provided, single submitter | clinical testing | The p.Y197S variant (also known as c.590A>C), located in coding exon 6 of the NBN gene, results from an A to C substitution at nucleotide position 590. The tyrosine at codon 197 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is 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. |