ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3818C>A (p.Pro1273Gln) (rs758355520)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668789 SCV000793447 likely pathogenic Wilson disease 2017-08-16 criteria provided, single submitter clinical testing
Invitae RCV000668789 SCV001222918 pathogenic Wilson disease 2019-11-28 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 1273 of the ATP7B protein (p.Pro1273Gln). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Wilson disease and has been shown to segregate with disease in a family (PMID: 16696937, 18483695, 25465132, 27398169). ClinVar contains an entry for this variant (Variation ID: 553360). This variant has been reported to affect ATP7B protein function (PMID:22692182). 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.Pro1273 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20485189, 23551039, 15024742, 17272994). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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