Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481451 | SCV000571009 | uncertain significance | not provided | 2016-07-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CHD2 gene. The R121L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R121L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CHD2-related disorder (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001364894 | SCV001561089 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2020-05-26 | 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 disruptive, 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 CHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 421719). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 121 of the CHD2 protein (p.Arg121Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. |