ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4339dup (p.Asp1447fs)

gnomAD frequency: 0.00001  dbSNP: rs1345677703
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000778398 SCV003233024 pathogenic Wilson disease 2023-08-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ATP7B protein in which other variant(s) (p.Arg1459Glyfs*2) have been determined to be pathogenic (PMID: 26799313). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 631704). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp1447Glyfs*2) in the ATP7B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the ATP7B protein.
Baylor Genetics RCV000778398 SCV004216426 likely pathogenic Wilson disease 2024-03-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000778398 SCV005430611 uncertain significance Wilson disease 2024-03-04 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 21 of the ATP7B gene, creating a frameshift and premature translation stop signal in the last coding exon. This mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. The clinical relevance of the loss of this C-terminal region is not known. To our knowledge, this variant has not been reported in individuals affected with Wilson disease in the literature. 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). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000778398 SCV005636586 likely pathogenic Wilson disease 2024-04-04 criteria provided, single submitter clinical testing

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