Submissions for variant NM_000053.4(ATP7B):c.1620C>T (p.Leu540=)

gnomAD frequency: 0.00150  dbSNP: rs145798966

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000244316	SCV000301695	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000244316	SCV000518709	likely benign	not specified	2018-02-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001086715	SCV000602599	benign	Wilson disease	2023-09-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086715	SCV000626831	benign	Wilson disease	2025-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000244316	SCV000694400	likely benign	not specified	2020-11-13	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000590083	SCV000704531	uncertain significance	not provided	2016-12-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590083	SCV001150661	likely benign	not provided	2024-12-01	criteria provided, single submitter	clinical testing	ATP7B: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001086715	SCV001268683	uncertain significance	Wilson disease	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001086715	SCV001977181	likely benign	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000244316	SCV002066453	likely benign	not specified	2017-10-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002401951	SCV002707377	likely benign	Inborn genetic diseases	2022-06-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV001086715	SCV004362494	uncertain significance	Wilson disease	2022-09-16	criteria provided, single submitter	clinical testing	This synonymous variant causes a C>T nucleotide change in exon 4 of the ATP7B gene. A functional RNA study has shown this variant causes exon 4 skipping (PMID: 33719328). This variant has been reported in individuals affected with Wilson disease (PMID: 27022412, 27982432) and ataxia (PMID: 27528516). This variant has been identified in 403/280870 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV001086715	SCV004846334	uncertain significance	Wilson disease	2024-02-05	criteria provided, single submitter	clinical testing	This synonymous variant causes a C>T nucleotide change in exon #4 of the ATP7B gene. A functional RNA study has shown this variant causes exon 4 skipping (PMID: 33719328). This variant has been reported in individuals affected with Wilson disease (PMID: 27022412, 27982432) and ataxia (PMID: 27528516). This variant has been identified in 403/280870 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV001086715	SCV001456186	likely benign	Wilson disease	2019-12-29	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000590083	SCV001807687	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000590083	SCV001929135	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000590083	SCV001963921	likely benign	not provided		no assertion criteria provided	clinical testing