Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000755928 | SCV000883606 | pathogenic | not provided | 2018-04-22 | criteria provided, single submitter | clinical testing | The CHD7 c.538C>T; p.Gln180Ter variant is reported in the literature as a de novo variant in CHARGE syndrome patients (Busa 2016, Lalani 2006), and it is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Busa T et al. Prenatal findings in children with early postnatal diagnosis of CHARGE syndrome. Prenat Diagn. 2016 Jun;36(6):561-7. Lalani SR et al. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet. 2006 Feb;78(2):303-14. |
| Illumina Laboratory Services, |
RCV001563584 | SCV001786557 | pathogenic | CHARGE association | 2020-11-16 | criteria provided, single submitter | clinical testing | The CHD7 c.538C>T (p.Gln180Ter) variant is a stop-gained variant that is predicted to result in a premature termination or absence of the protein. The p.Gln180Ter variant has been reported in at least two studies, in which it is found in a heterozygous state in two individuals with CHARGE syndrome. In both these individuals the variant was identified in a de novo state (Lalani et al. 2006; Busa et al. 2016). The p.Gln180Ter variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Based on the predicted truncating nature of the variant, its identification in a de novo state, and its rarity, the p.Gln180Ter variant is classified as pathogenic for CHD7 disorder. |