Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014641 | SCV001175374 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-17 | criteria provided, single submitter | clinical testing | The p.E726K variant (also known as c.2176G>A), located in coding exon 14 of the NBN gene, results from a G to A substitution at nucleotide position 2176. The glutamic acid at codon 726 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly 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 | RCV001307900 | SCV001497328 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 726 of the NBN protein (p.Glu726Lys). 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: 820820). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Genome- |
RCV001307900 | SCV002046039 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing |