ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2998G>A (p.Gly1000Arg)

gnomAD frequency: 0.00001  dbSNP: rs751078884
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673544 SCV000798757 likely pathogenic Wilson disease 2018-03-23 criteria provided, single submitter clinical testing
Invitae RCV000673544 SCV000935825 pathogenic Wilson disease 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1000 of the ATP7B protein (p.Gly1000Arg). This variant is present in population databases (rs751078884, gnomAD 0.007%). This missense change has been observed in individual(s) with Wilson disease (PMID: 31059521). ClinVar contains an entry for this variant (Variation ID: 557405). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 20333758). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000673544 SCV001977143 likely pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Arcensus RCV000673544 SCV002564616 likely pathogenic Wilson disease 2013-02-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000673544 SCV002780465 likely pathogenic Wilson disease 2021-10-14 criteria provided, single submitter clinical testing
GeneDx RCV003319396 SCV004023789 pathogenic not provided 2023-08-03 criteria provided, single submitter clinical testing Published functional studies found this variant is unable to rescue growth of a yeast strain deficient for ccc2 (the ATP7B otholog in yeast) (Luoma LM et al., 2010); Not observed at 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: 16088907, 30120852, 20333758, 30275481, 22692182, 31708252, 23486543)

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