ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4090_4091GT[1] (p.Ser1365fs) (rs771603301)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000410145 SCV000593530 pathogenic Wilson disease 2016-02-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000410145 SCV000694462 pathogenic Wilson disease 2017-02-28 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.4092_4093delGT (p.Ser1365Cysfs) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool, Mutation Taster, predicts a damaging outcome for this variant. This variant is absent in the large control population database ExAC (0/108958 control chromosomes). One clinical diagnostic laboratories and multiple reputable databases classified this variant as pathogenic. In addition, the variant has been reported in numerous patients in the literature. Taken together, this variant is classified as pathogenic.
Invitae RCV000410145 SCV001209905 pathogenic Wilson disease 2019-12-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ATP7B gene (p.Ser1365Cysfs*12). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 101 amino acids of the ATP7B protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 17317524, 20042865). ClinVar contains an entry for this variant (Variation ID: 371438). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the ATP7B protein. Other variant(s) that disrupt this region (p.Gln1399Argfs*6) have been determined to be pathogenic (PMID: 11054498, 14748773, 28600779). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000410145 SCV000487020 pathogenic Wilson disease 2016-09-23 no assertion criteria provided clinical testing
GenomeConnect, ClinGen RCV000410145 SCV000840281 not provided Wilson disease no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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