Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002785911 | SCV003020347 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-09-23 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1986072). 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 isoleucine, which is neutral and non-polar, at codon 549 of the NBN protein (p.Lys549Ile). |
| Ambry Genetics | RCV004064730 | SCV005019336 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-25 | criteria provided, single submitter | clinical testing | The p.K549I variant (also known as c.1646A>T), located in coding exon 11 of the NBN gene, results from an A to T substitution at nucleotide position 1646. The lysine at codon 549 is replaced by isoleucine, 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. |
| Baylor Genetics | RCV004571251 | SCV005056118 | uncertain significance | Aplastic anemia | 2024-03-20 | criteria provided, single submitter | clinical testing |