ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.802_808del (p.Cys268fs) (rs1566598496)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780938 SCV000918607 pathogenic Wilson disease 2018-11-15 criteria provided, single submitter clinical testing Variant summary: ATP7B c.802_808delTGTAAGT (p.Cys268LeufsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Ser382fsX24, p.Gln511X, p.Ile582fsX25). The variant was absent in 244586 control chromosomes (gnomAD). c.802_808delTGTAAGT has been reported in the literature in an individual affected with Wilson Disease (Haas_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001008091 SCV001167836 pathogenic not provided 2018-11-30 criteria provided, single submitter clinical testing The c.802_808delTGTAAGT variant in the ATP7B gene has been reported previously in the heterozygous state with a second ATP7B variant in a patient with Wilson disease (Haas et al., 1999). The c.802_808delTGTAAGT variant causes a frameshift starting with codon Cysteine 268, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Cys268LeufsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.802_808delTGTAAGT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.802_808delTGTAAGT as a pathogenic variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.