Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000296349 | SCV000329255 | uncertain significance | not provided | 2016-03-11 | criteria provided, single submitter | clinical testing | The S62N variant in the CHD2 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The S62N variant 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 S62N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across mammalian species; in silico is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S62N as a variant of unknown significance. |
Revvity Omics, |
RCV003144187 | SCV003831923 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2022-06-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003144187 | SCV005734718 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2024-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 62 of the CHD2 protein (p.Ser62Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 279756). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CHD2 protein function with a negative predictive value of 95%. 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. |