ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.778dup (p.Gln260fs)

dbSNP: rs786204570
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169312 SCV000220636 likely pathogenic Wilson disease 2014-08-26 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169312 SCV000694470 pathogenic Wilson disease 2017-02-14 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.778dupC (p.Gln260Profs) 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. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (e.g. c.813delC (p.Cys271fs), c.845delT (p.Leu282fs), and c.1145_1151delCCCAACT (p.Ser382fs)). Mutation taster predicts a damaging outcome for this variant. This variant is absent in 120078 control chromosomes, while it was reported in multiple Wilson disease patients indicating pathogenicity. Moreover, HGMD lists several variants affecting the same codon indicating the variant to be located in a mutational hotspot and further supporting pathogenicity. One clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000169312 SCV000752251 pathogenic Wilson disease 2023-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln260Profs*10) 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 present in population databases (rs786204570, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 10980554, 11216666, 19172127, 20082719). This variant is also known as 777insC, 778insC, or 779insC. ClinVar contains an entry for this variant (Variation ID: 188938). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001560289 SCV001782669 pathogenic not provided 2021-08-04 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease This variant is associated with the following publications: (PMID: 10980554, 19172127, 11216666, 20082719)
Genome-Nilou Lab RCV000169312 SCV001977397 pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001560289 SCV002525829 likely pathogenic not provided 2021-11-08 criteria provided, single submitter clinical testing PM2, PVS1
Fulgent Genetics, Fulgent Genetics RCV000169312 SCV002785210 pathogenic Wilson disease 2021-09-03 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000169312 SCV004099059 likely pathogenic Wilson disease 2023-08-23 criteria provided, single submitter clinical testing PVS1, PM2
Baylor Genetics RCV000169312 SCV004216438 pathogenic Wilson disease 2023-04-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001560289 SCV004701957 pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing ATP7B: PVS1, PM2
GenomeConnect, ClinGen RCV000169312 SCV000986857 not provided Wilson disease no assertion provided phenotyping only Variant interpretted as pathogenic and reported on 07/25/2018 by GTR ID PerkinElmer Genetics, Inc.. 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.
Natera, Inc. RCV000169312 SCV002087895 pathogenic Wilson disease 2020-09-21 no assertion criteria provided clinical testing
Genomics And Bioinformatics Analysis Resource, Columbia University RCV000169312 SCV004024121 pathogenic Wilson disease no assertion criteria provided research

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