Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Human Genetics, |
RCV000659301 | SCV000781109 | pathogenic | CHARGE syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000659301 | SCV001582550 | pathogenic | CHARGE syndrome | 2022-03-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 547195). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This premature translational stop signal has been observed in individual(s) with CHARGE syndrome (PMID: 15300250, 26538304). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2024*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). |
| Gene |
RCV001557861 | SCV001779705 | pathogenic | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 15300250, 35938004, 31785789, 26538304) |
| Ambry Genetics | RCV004026047 | SCV004923872 | pathogenic | Inborn genetic diseases | 2023-11-13 | criteria provided, single submitter | clinical testing | The c.6070C>T (p.R2024*) alteration, located in exon 30 (coding exon 29) of the CHD7 gene, consists of a C to T substitution at nucleotide position 6070. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 2024. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple individuals with features consistent with CHARGE syndrome (Vissers, 2004; Legendre, 2012), including multiple de novo occurrences (Jongmans, 2009; Wessels, 2010; Wu, 2022). Based on the available evidence, this alteration is classified as pathogenic. |