ClinVar Miner

Submissions for variant NM_000053.3(ATP7B):c.3895C>T (p.Leu1299Phe) (rs749472361)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169572 SCV000221072 likely pathogenic Wilson disease 2015-01-22 criteria provided, single submitter literature only
Invitae RCV000169572 SCV000626861 pathogenic Wilson disease 2017-07-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 1299 of the ATP7B protein (p.Leu1299Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs749472361, ExAC 0.04%). This variant has been reported as homozygous or in combination with another ATP7B variant in seven individuals affected with Wilson disease (PMID: 24094725). It was also reported in individuals affected with Wilson disease where the second allele was not reported (PMID: 17264425, 23235335, 23551039, 17823867, 27022412). ClinVar contains an entry for this variant (Variation ID: 189149). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individuals with Kayser-Fleischer rings and plasma ceruloplasmin <= 20 mg/dL, findings that are highly specific for Wilson disease (PMID: 24094725). For these reasons, this variant has been classified as Pathogenic.

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