Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471976 | SCV002767669 | uncertain significance | CHARGE syndrome | 2020-05-25 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_017780.2(CHD7):c.6638C>G in exon 31 of 38 of the CHD7 gene (NB: this variant is non-coding in an alternative transcript). This substitution is predicted to create a major amino acid change from a serine to a cysteine at position 2213 of the protein; NP_060250.2(CHD7):p.(Ser2213Cys). The serine at this position has low conservation (100 vertebrates, UCSC), and is not situated in a known functional domain (NCBI). In silico software predicts this variant to be tolerated (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database. An alternative residue change at the same location has been reported in the gnomAD database at a frequency of 0.0005%. This variant has not previously been reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VUS with LOW CLINICAL RELEVANCE. |
| Labcorp Genetics |
RCV002471976 | SCV005754183 | uncertain significance | CHARGE syndrome | 2024-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2213 of the CHD7 protein (p.Ser2213Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHD7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1805558). 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 CHD7 protein function with a negative predictive value of 80%. 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. |