ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.3782G>T (p.Trp1261Leu)

dbSNP: rs1555444603
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497985 SCV000589707 pathogenic not provided 2022-02-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31618753)
Institute of Human Genetics, University of Leipzig Medical Center RCV001253722 SCV001429574 likely pathogenic Developmental and epileptic encephalopathy 94 2017-11-16 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed).
Eurofins-Biomnis RCV001253722 SCV003935122 pathogenic Developmental and epileptic encephalopathy 94 2022-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001253722 SCV004641621 pathogenic Developmental and epileptic encephalopathy 94 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 1261 of the CHD2 protein (p.Trp1261Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CHD2-related conditions (PMID: 31618753). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 432036). 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 expected to disrupt CHD2 protein function with a positive predictive value of 95%. This variant disrupts the p.Trp1261 amino acid residue in CHD2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 34713950; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GenomeConnect - Simons Searchlight RCV001265453 SCV001443585 likely pathogenic Complex neurodevelopmental disorder 2016-05-04 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2016-05-04 and interpreted as Likely Pathogenic. Variant was initially reported on 2016-01-18 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
Revvity Omics, Revvity RCV001253722 SCV003831919 uncertain significance Developmental and epileptic encephalopathy 94 2021-04-30 flagged submission clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.