ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.399G>A (p.Trp133Ter)

gnomAD frequency: 0.00001  dbSNP: rs1033235740
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174890 SCV001338313 likely pathogenic Wilson disease 2020-02-18 criteria provided, single submitter clinical testing Variant summary: ATP7B c.399G>A (p.Trp133X) 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 249318 control chromosomes (gnomAD). To our knowledge, no occurrence of c.399G>A in individuals affected with Wilson Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001174890 SCV002229233 pathogenic Wilson disease 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp133*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 917710). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001174890 SCV002787100 likely pathogenic Wilson disease 2022-05-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV001174890 SCV004216373 pathogenic Wilson disease 2023-07-22 criteria provided, single submitter clinical testing

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