Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001034829 | SCV001198128 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2019-04-04 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NBN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 338 of the NBN protein (p.Pro338Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. |
Ambry Genetics | RCV003346256 | SCV004051402 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-06 | criteria provided, single submitter | clinical testing | The p.P338T variant (also known as c.1012C>A), located in coding exon 9 of the NBN gene, results from a C to A substitution at nucleotide position 1012. The proline at codon 338 is replaced by threonine, an amino acid with highly 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. |