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

gnomAD frequency: 0.00005  dbSNP: rs121908000

Total submissions: 13

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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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.
Eurofins Ntd Llc (ga)	RCV000597397	SCV000700799	pathogenic	not provided	2016-11-11	criteria provided, single submitter	clinical testing
Invitae	RCV000004069	SCV000963831	pathogenic	Wilson disease	2024-01-01	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 708 of the ATP7B protein (p.Leu708Pro). This variant is present in population databases (rs121908000, gnomAD 0.007%). This missense change has been observed in individual(s) with Wilson disease (PMID: 9311736, 11093740, 15024742). It is commonly reported in individuals of Canary Islands and Brazil ancestry (PMID: 9311736, 11093740, 15024742). ClinVar contains an entry for this variant (Variation ID: 3865). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV000597397	SCV001714447	pathogenic	not provided	2019-07-29	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000004069	SCV001977351	pathogenic	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000597397	SCV002512866	pathogenic	not provided	2020-03-06	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22692182, 23982005, 11093740, 21832955, 9311736, 15024742, 32154060)
Fulgent Genetics, Fulgent Genetics	RCV000004069	SCV002809748	pathogenic	Wilson disease	2021-08-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000004069	SCV004216281	pathogenic	Wilson disease	2023-10-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000004069	SCV004238421	pathogenic	Wilson disease	2023-03-31	criteria provided, single submitter	clinical testing
OMIM	RCV000004069	SCV000024235	pathogenic	Wilson disease	2000-12-01	no assertion criteria provided	literature only
Natera, Inc.	RCV000004069	SCV001463840	pathogenic	Wilson disease	2020-09-16	no assertion criteria provided	clinical testing