ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3955C>T (p.Arg1319Ter) (rs193922109)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000029377 SCV000052025 pathogenic Wilson disease 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Genetic Services Laboratory, University of Chicago RCV000029377 SCV000192356 pathogenic Wilson disease 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000494120 SCV000582410 pathogenic not provided 2018-11-13 criteria provided, single submitter clinical testing The R1319X variant in the ATP7B gene has been reported previously in association with Wilson disease, when present in the homozygous state or when in trans with another disease-causing variant (Waldenström et al., 1996; Abdelghaffar et al., 2008; Paradisi et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1319X variant is observed in 1/11572 (0.009%) alleles from individuals of Latino background and in 4/66738 (0.006%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). We interpret R1319X as a pathogenic variant.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000029377 SCV000602617 pathogenic Wilson disease 2019-05-06 criteria provided, single submitter clinical testing The ATP7B c.3955C>T; p.Arg1319Ter variant (rs193922109) is described in the medical literature in individuals with Wilson disease (Deguti 2004, Margarit 2005, Waldenstrom 1996). The variant is listed as pathogenic by several sources in the ClinVar database (Variation ID: 35728). This variant is found in the general population in 21 out of 277212 alleles in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Deguti MM et al. Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients. Hum Mutat. 2004 Apr;23(4):398. Margarit E et al. Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet. 2005 Jul;68(1):61-8. Waldenstrom E et al. Efficient detection of mutations in Wilson disease by manifold sequencing. Genomics. 1996 Nov 1;37(3):303-9.
Fulgent Genetics,Fulgent Genetics RCV000029377 SCV000611175 pathogenic Wilson disease 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000029377 SCV000626862 pathogenic Wilson disease 2019-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1319*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs193922109, ExAC 0.009%). This variant has been reported as homozygous and in combination with other pathogenic ATP7B variants in individuals and families affected with Wilson disease (PMID: 21682854, 18483695, 7626145, 893844, 23518715, 27022412, 21796144, 15024742, 15952988). ClinVar contains an entry for this variant (Variation ID: 35728). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 16283883, 10441329). For these reasons, this variant has been classified as Pathogenic.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000029377 SCV000746793 pathogenic Wilson disease 2017-12-18 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000029377 SCV000782701 pathogenic Wilson disease 2017-06-21 criteria provided, single submitter clinical testing
Counsyl RCV000029377 SCV000220371 pathogenic Wilson disease 2015-07-14 no assertion criteria provided clinical testing

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