Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002036607 | SCV002317635 | uncertain significance | Cernunnos-XLF deficiency | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 178 of the NHEJ1 protein (p.Arg178Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NHEJ1-related conditions. 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. Experimental studies have shown that this missense change does not substantially affect NHEJ1 function (PMID: 25661488). 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. |
Breakthrough Genomics, |
RCV004694164 | SCV005188292 | uncertain significance | not provided | criteria provided, single submitter | not provided |