ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2953T>C (p.Cys985Arg) (rs193922104)

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Total submissions: 5
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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 RCV000029360 SCV000052007 likely pathogenic Wilson disease 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726685 SCV000702099 likely pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing
Invitae RCV000029360 SCV000942688 uncertain significance Wilson disease 2019-06-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 985 of the ATP7B protein (p.Cys985Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATP7B-related disease. ClinVar contains an entry for this variant (Variation ID: 35711). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000029360 SCV001473835 uncertain significance Wilson disease 2019-12-12 criteria provided, single submitter clinical testing The ATP7B c.2953T>C; p.Cys985Arg variant (rs193922104), to our knowledge, is not reported in the medical literature. However, another variant in the same codon, p.Cys985Tyr, is described in an individual with suspected Wilson disease who also carried an additional pathogenic variant (Haas 1999). The p.Cys985Arg variant is reported in the ClinVar database (Variation ID: 35711) and in the general population with an overall allele frequency of 0.001% (4/280672 alleles) in the Genome Aggregation Database. The cysteine at codon 985 is highly conserved, is located in the transmembrane domain, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Cys985Arg variant is uncertain at this time. References: Haas R et al. Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online. Hum Mutat. 1999;14(1):88.
Mayo Clinic Laboratories, Mayo Clinic RCV000726685 SCV001715053 likely pathogenic not provided 2019-07-08 criteria provided, single submitter clinical testing PM2, PM3, PP1, PP4,

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