Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001236570 | SCV001409299 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-07-23 | 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. 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 methionine with isoleucine at codon 294 of the NBN protein (p.Met294Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. |
Ambry Genetics | RCV002447181 | SCV002682710 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-24 | criteria provided, single submitter | clinical testing | The p.M294I variant (also known as c.882G>C), located in coding exon 7 of the NBN gene, results from a G to C substitution at nucleotide position 882. The methionine at codon 294 is replaced by isoleucine, an amino acid with highly 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. |
Baylor Genetics | RCV003473810 | SCV004199658 | uncertain significance | Aplastic anemia | 2023-05-24 | criteria provided, single submitter | clinical testing |