Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001067645 | SCV001232714 | pathogenic | Wilson disease | 2019-11-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant has been observed in combination with another ATP7B variant in an individual affected with Wilson disease (PMID: 10544227). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr741*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. |
| Genome- |
RCV001067645 | SCV001977341 | pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001067645 | SCV002074154 | pathogenic | Wilson disease | 2022-01-09 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.2223T>A (p.Tyr741X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249592 control chromosomes. c.2223T>A has been reported in the literature in individuals affected with Wilson Disease (example, Loudianos_1999, Simon_2008, Weiss_2010). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| All of Us Research Program, |
RCV001067645 | SCV004827014 | pathogenic | Wilson disease | 2023-11-20 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 8 of the ATP7B gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in individuals affected with autosomal recessive Wilson disease (PMID: 10544227, 18416466, 20517649, 27022412, 34470610), including in one individual in the compound heterozygous state with a second pathogenic variant in the ATP7B gene (PMID: 10544227) and in two individuals in unknown phase with a second pathogenic variant in the ATP7B gene (PMID: 18416466, 20517649). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATP7B function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |