ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2123T>C (p.Leu708Pro) (rs121908000)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000004069 SCV000192319 pathogenic Wilson disease 2013-02-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507833 SCV000602615 pathogenic not specified 2017-02-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000004069 SCV000694413 pathogenic Wilson disease 2016-08-11 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.2123T>C (p.Leu708Pro) variant involves the alteration of a conserved nucleotide located in the transmembrane domain of ATB7B. 3/4 in silico tools predict a damaging outcome for this substitution. This variant is absent in 120120 control chromosomes while it was observed in several Wilson Disease patient in either homozygosity or heterozygosity indicating the variant to be pathogenic. Moreover, it is considered to be a founder mutation in the Canary Islands representing about 50% of the WD allele in this population. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000597397 SCV000700799 pathogenic not provided 2016-11-11 criteria provided, single submitter clinical testing
Invitae RCV000004069 SCV000963831 pathogenic Wilson disease 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 708 of the ATP7B protein (p.Leu708Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another ATP7B variant in several individuals and families affected with Wilson disease and is considered a founder mutation in the Canary Islands and Brazil (PMID: 11093740, 15024742, 9311736). ClinVar contains an entry for this variant (Variation ID: 3865). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004069 SCV000024235 pathogenic Wilson disease 2000-12-01 no assertion criteria provided literature only

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