Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000548285 | SCV000631259 | pathogenic | CHARGE syndrome | 2019-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1810*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). This variant has been reported in the literature in individuals affected with CHARGE syndrome (PMID: 16400610, 26538304, 18445044). In several of these individuals, the variant was shown to be de novo (PMID: 16400610). ClinVar contains an entry for this variant (Variation ID: 459555). This variant is not present in population databases (ExAC no frequency). |
Gene |
RCV000599382 | SCV000709800 | pathogenic | not provided | 2023-07-27 | 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26538304, 16400610, 33100332, 18445044, 35938004, 29261186, 25525159) |
Provincial Medical Genetics Program of British Columbia, |
RCV000548285 | SCV002320801 | pathogenic | CHARGE syndrome | 2022-01-01 | criteria provided, single submitter | clinical testing | |
3billion | RCV000548285 | SCV004013828 | pathogenic | CHARGE syndrome | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. It is a stop-gained (nonsense) variant predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000459555/PMID: 16400610). This variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. | |
Rady Children's Institute for Genomic Medicine, |
RCV000548285 | SCV004046360 | pathogenic | CHARGE syndrome | criteria provided, single submitter | clinical testing | This nonsense variant found in exon 26 of 38 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in patients with CHARGE syndrome, as a de novo change or of unknown inheritance (PMID: 16400610, 26538304, 18445044). It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.5428C>T (p.Arg1810Ter) variant is classified as Pathogenic. | |
Juno Genomics, |
RCV000548285 | SCV005416355 | pathogenic | CHARGE syndrome | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PM6+PS4_Supporting+PP4 | |
Prevention |
RCV004748818 | SCV005361256 | pathogenic | CHD7-related disorder | 2024-07-19 | no assertion criteria provided | clinical testing | The CHD7 c.5428C>T variant is predicted to result in premature protein termination (p.Arg1810*). This variant has been reported as de novo in multiple individuals with CHD7-related disorders (Lalani et al. 2006. PubMed ID: 16400610; Wincent et al 2008. PubMed ID: 18445044; Sohn et al. 2016. PubMed ID: 26538304; Boissel et al. 2017. PubMed ID: 29261186). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in CHD7 are expected to be pathogenic. This variant is interpreted as pathogenic. |