Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001061115 | SCV001225847 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2023-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1691 of the CHD2 protein (p.Pro1691Ser). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHD2 protein function. ClinVar contains an entry for this variant (Variation ID: 855780). This variant has not been reported in the literature in individuals affected with CHD2-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Neuberg Centre For Genomic Medicine, |
RCV001061115 | SCV004047936 | uncertain significance | Developmental and epileptic encephalopathy 94 | criteria provided, single submitter | clinical testing | The missense variant c.5071C>T(p.Pro1691Ser) in CHD2 gene has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Pro1691Ser variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Pro at position 1691 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. This variant has not been reported to the ClinVar database. In silico tools predict the variant to be tolerated. The residue is conserved across species. The amino acid change p.Pro1691Ser in CHD2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance. | |
| Prevention |
RCV004735951 | SCV005357249 | uncertain significance | CHD2-related disorder | 2024-03-30 | no assertion criteria provided | clinical testing | The CHD2 c.5071C>T variant is predicted to result in the amino acid substitution p.Pro1691Ser. To our knowledge, this variant has not been reported in the literature or in a large population database , indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |