ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3247C>T (p.Leu1083Phe)

dbSNP: rs1286080173
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Total submissions: 7
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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 RCV000586978 SCV000694441 pathogenic Wilson disease 2016-11-21 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.3247C>T (p.Leu1083Phe) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 120420 control chromosomes but was reported at high frequency in Korean WD patients, and also in Japanese WD patients. Functionally, the variant was shown to lead to significant abnormalities subcellular localization and protein level. Taken together, this variant is classified as pathogenic.
Genome-Nilou Lab RCV000586978 SCV001977262 likely pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV002223878 SCV002502179 likely pathogenic not provided 2022-03-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000586978 SCV003442169 pathogenic Wilson disease 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1083 of the ATP7B protein (p.Leu1083Phe). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with Wilson disease (PMID: 9554743, 11954751, 26466587). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 495412). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7B protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 22240481, 22692182). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000586978 SCV004216431 pathogenic Wilson disease 2023-05-02 criteria provided, single submitter clinical testing
Counsyl RCV000586978 SCV001132129 likely pathogenic Wilson disease 2019-06-27 no assertion criteria provided clinical testing
Natera, Inc. RCV000586978 SCV001455592 pathogenic Wilson disease 2020-09-16 no assertion criteria provided clinical testing

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