ClinVar Miner

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

dbSNP: rs1345677703
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778398 SCV000914627 uncertain significance Wilson disease 2018-12-12 criteria provided, single submitter clinical testing The ATP7B c.4339dupG (p.Asp1447GlyfsTer2) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database. This variant is located in the last exon and may escape nonsense-mediated decay. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for Wilson disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000778398 SCV003233024 pathogenic Wilson disease 2023-08-06 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 631704). 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. For these reasons, this variant has been classified as Pathogenic. 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 2023-05-05 criteria provided, single submitter clinical testing

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