ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1523G>C (p.Arg508Thr)

gnomAD frequency: 0.00003  dbSNP: rs578173224
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240008 SCV001412923 uncertain significance Wilson disease 2022-06-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 508 of the ATP7B protein (p.Arg508Thr). This variant is present in population databases (rs578173224, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 965532). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV001240008 SCV002783248 uncertain significance Wilson disease 2024-03-06 criteria provided, single submitter clinical testing
GeneDx RCV003317463 SCV004021674 uncertain significance not provided 2023-07-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified as a secondary finding in an individual who underwent whole exome sequencing (Chetruengchai W and Shotelersuk V. 2022); This variant is associated with the following publications: (PMID: 34621001)
All of Us Research Program, National Institutes of Health RCV001240008 SCV004824918 uncertain significance Wilson disease 2024-01-03 criteria provided, single submitter clinical testing This missense variant replaces arginine with threonine at codon 508 of the ATP7B protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has been identified in 29/280492 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001240008 SCV002087874 uncertain significance Wilson disease 2020-02-26 no assertion criteria provided clinical testing

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