Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059176 | SCV001223789 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2019-02-20 | 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 glutamine with leucine at codon 39 of the NBN protein (p.Gln39Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. |
Ambry Genetics | RCV002327330 | SCV002627698 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | The p.Q39L variant (also known as c.116A>T), located in coding exon 2 of the NBN gene, results from an A to T substitution at nucleotide position 116. The glutamine at codon 39 is replaced by leucine, an amino acid with dissimilar 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. |