ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3301G>A (p.Gly1101Arg) (rs786204483)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169142 SCV000220362 likely pathogenic Wilson disease 2014-05-30 criteria provided, single submitter literature only
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000169142 SCV001158354 likely pathogenic Wilson disease 2019-04-06 criteria provided, single submitter clinical testing The ATP7B c.3301G>A; p.Gly1101Arg variant (rs786204483) is reported in two individuals with Wilson disease who are homozygous for the variant (reported as G1102R in Thomas 1995). Functional assays show the variant protein is unable to complement ccc2 function under low iron conditions, supportive of it being deleterious. (Luoma 2010). This variant is reported in ClinVar (Variation ID: 188808). It is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 1101 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. REFERENCES Luoma LM et al. Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B. Hum Mutat. 2010 May;31(5):569-77. Thomas GR et al. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210-7.
Invitae RCV000169142 SCV001400226 pathogenic Wilson disease 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1101 of the ATP7B protein (p.Gly1101Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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 individuals affected with Wilson disease (PMID: 7626145, 23551039, 31059521). ClinVar contains an entry for this variant (Variation ID: 188808). This variant has been reported to affect ATP7B protein function (PMID: 20333758). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV000169142 SCV001424371 pathogenic Wilson disease criteria provided, single submitter clinical testing

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