Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001236948 | SCV001409689 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 747 of the NBN protein (p.Asn747Ile). 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: 962992). 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. |
Ambry Genetics | RCV002430012 | SCV002727967 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-18 | criteria provided, single submitter | clinical testing | The p.N747I variant (also known as c.2240A>T), located in coding exon 16 of the NBN gene, results from an A to T substitution at nucleotide position 2240. The asparagine at codon 747 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. |