ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2383C>T (p.Leu795Phe) (rs751710854)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169151 SCV000220376 likely pathogenic Wilson disease 2014-06-04 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000169151 SCV000694422 pathogenic Wilson disease 2016-06-07 criteria provided, single submitter clinical testing Variant summary: The c.2383C>T (p.Leu795Phe) in ATP7B gene is a missense change that involves a conserved nucleotide and 4/5 in silico tools predict deleterious outcome. The variant is present in the control population dataset of ExAC at frequency of 0.00003 (4/120764 chrs tested). The observed frequency does not exceed the maximum expected allele frequency for a pathogenic variant of 0.0054. The variant was identified homozygously and in compound heterozygosity in several WD pts. In functional studies the variant displayed features of mild mutation. The variant of interest has been reported as Likely Pathogenic by another clinical laboratory, without evidence to independently evaluate. Taking together, the variant was classified as Pathogenic.
Invitae RCV000169151 SCV000815245 pathogenic Wilson disease 2018-12-09 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 795 of the ATP7B protein (p.Leu795Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs751710854, ExAC 0.01%). This variant has been observed to be homozygous and in combination with another ATP7B variant in several individuals affected with Wilson disease (WD) (PMID: 23551039, 17264425). This variant has been observed in additional individuals with WD (PMID: 9311736, 23235335, 24094725, 26207595, 27022412). ClinVar contains an entry for this variant (Variation ID: 188814). 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 C15"). For these reasons, this variant has been classified as Pathogenic.
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000169151 SCV001133003 pathogenic Wilson disease 2019-09-15 no assertion criteria provided clinical testing

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