Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001373822 | SCV001570554 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-05-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 47 of the NBN protein (p.Val47Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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). |
Natera, |
RCV001373822 | SCV002078687 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-02-16 | no assertion criteria provided | clinical testing |