ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3029A>G (p.Lys1010Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001236933 SCV001409674 likely pathogenic Wilson disease 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 1010 of the ATP7B protein (p.Lys1010Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs747584649, ExAC 0.01%). This variant has been observed o be homozygous in individuals affected with Wilson disease and has been shown to segregate with disease in a family (PMID: 17264425, 18698682, 30120852). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Lys1010 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been observed in individuals with ATP7B-related conditions (PMID: 11721763), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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