Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014405 | SCV001175105 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | The p.K698E variant (also known as c.2092A>G), located in coding exon 14 of the NBN gene, results from an A to G substitution at nucleotide position 2092. The lysine at codon 698 is replaced by glutamic acid, 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 | RCV003617875 | SCV004388478 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-01-11 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 820700). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 698 of the NBN protein (p.Lys698Glu). |