Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659300 | SCV000781108 | likely pathogenic | CHARGE syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000659300 | SCV001395181 | pathogenic | CHARGE syndrome | 2019-04-25 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 27 of the CHD7 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with CHARGE syndrome (PMID: 22461308). ClinVar contains an entry for this variant (Variation ID: 547194). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002249389 | SCV002520087 | pathogenic | not provided | 2022-05-17 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22461308, 29304373) |
Baylor Genetics | RCV000659300 | SCV004041300 | pathogenic | CHARGE syndrome | 2023-06-10 | criteria provided, single submitter | clinical testing |