Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003486496 | SCV004241347 | likely pathogenic | CHARGE syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | Variant summary: CHD7 c.5436C>G (p.Asp1812Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248324 control chromosomes (gnomAD). c.5436C>G has been reported in the literature in at least two individuals affected with and/or with clinical features of CHARGE Syndrome, including one case where it was reportedly de novo (e.g. Bilan_2012, Butcher_2017). These data indicate the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, other variants affecting the same amino acid have been reported in association with CHARGE syndrome in the HGMD database, suggesting Asp1812 may be important for protein function. The following publications have been ascertained in the context of this evaluation (PMID: 29304373, 22033296, 28475860, 35904121). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |