ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3305T>C (p.Ile1102Thr) (rs560952220)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000495835 SCV000694443 pathogenic Wilson disease 2020-09-21 criteria provided, single submitter clinical testing Variant summary: ATP7B c.3305T>C (p.Ile1102Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249578 control chromosomes (gnomAD). c.3305T>C has been reported in the literature in multiple individuals affected with Wilson Disease (example: Butler_2001, Kumar_2007, Dastsooz_2013). These data indicate that the variant is very likely to be associated with disease. In a yeast complementation functional assay, the variant was found to have intermediate to severe deficit (Luoma_2010). One other ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Centogene AG - the Rare Disease Company RCV000495835 SCV001424370 pathogenic Wilson disease criteria provided, single submitter clinical testing
Invitae RCV000495835 SCV001583735 pathogenic Wilson disease 2020-06-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1102 of the ATP7B protein (p.Ile1102Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs560952220, ExAC 0.006%). This variant has been observed to be homozygous in or in combination with another ATP7B variant in several individuals affected with Wilson disease (PMID: 30980273, 7626145, 24003324). It is also known as Ile1103Thr in the literature. ClinVar contains an entry for this variant (Variation ID: 430725). This variant has been reported to affect ATP7B protein function (PMID: 20333758). For these reasons, this variant has been classified as Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000495835 SCV000583503 likely pathogenic Wilson disease no assertion criteria provided clinical testing The observed mutation is reported in 1000 genomes and ExAC databases. Its dbSNP reference number is rs560952220. The in silico prediction of the observed mutation is disease-causing by Mutationtaster2 and probably damaging by PolyPhen2 and SIFT. The proband, born of a non consanguinous union was clinically diagnosed to be affected with Wilson's disease. Upon investigation it was found that the proband had c.3305T>C (p.I1102T) mutation in exon 15 of ATP7B gene. His parents were further investigated for the same mutation and were found to be heterozyous for the same by Sanger sequencing. Also during subsequent pregnancy the fetus was found to be heterozygous for the same mutation.
Counsyl RCV000495835 SCV001132340 pathogenic Wilson disease 2015-09-24 no assertion criteria provided clinical testing

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.