Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145684 | SCV000192790 | likely pathogenic | CHARGE association | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Genomic Diagnostic Laboratory, |
RCV000145684 | SCV000328346 | likely pathogenic | CHARGE association | 2016-09-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000145684 | SCV004324322 | pathogenic | CHARGE association | 2023-09-27 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with CHARGE syndrome (PMID: 16400610). In at least one individual the variant was observed to be de novo. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2096 of the CHD7 protein (p.His2096Arg). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 158309). 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 CHD7 protein function. Experimental studies have shown that this missense change affects CHD7 function (PMID: 20453063). For these reasons, this variant has been classified as Pathogenic. |