ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3045G>A (p.Leu1015=) (rs1801248)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029365 SCV000052012 benign Wilson disease 2011-08-18 criteria provided, single submitter clinical testing Converted during submission to Benign.
Genetic Services Laboratory, University of Chicago RCV000145268 SCV000192338 benign not specified 2013-02-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000145268 SCV000301712 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029365 SCV000384662 benign Wilson disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000145268 SCV000517725 benign not specified 2016-02-08 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 RCV000029365 SCV000602586 benign Wilson disease 2020-08-20 criteria provided, single submitter clinical testing
Institute for Genomic Medicine, Nationwide Children's Hospital RCV000029365 SCV001571615 likely pathogenic Wilson disease 2021-04-20 criteria provided, single submitter research The c.3045G>A variant is predicted to encode a synonymous change (p.Leu1015Leu) in exon 13 of ATP7B. The prevalence of this variant in the gnomAD database (MAF=0.02544, 126 homozygotes) suggests that it is far too common to cause disease in homozygous state. However, we identified this variant in compound-heterozygous state with a well-established pathogenic truncating variant (p.Arg1319*). Research RNA-seq of proband liver tissue established that the p.Leu1015Leu variant causes exon 13 skipping in approximately 1/3 of transcripts. We propose that this variant is a hypomorphic allele that only causes disease when compound-heterozygous with a loss-of-function variant. We therefore interpret the p.Leu1015Leu variant as likely pathogenic.
Invitae RCV000029365 SCV001723341 benign Wilson disease 2020-12-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV000029365 SCV001459709 benign Wilson disease 2020-09-16 no assertion criteria provided clinical testing

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