ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3426G>C (p.Gln1142His) (rs778749563)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409630 SCV000485394 likely pathogenic Wilson disease 2015-12-02 criteria provided, single submitter clinical testing
Invitae RCV000409630 SCV000934021 uncertain significance Wilson disease 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1142 of the ATP7B protein (p.Gln1142His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs778749563, ExAC 0.03%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with Wilson disease (PMID: 11405812). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. It has also been reported in other unrelated affected individuals (PMID: 26483271, 11043508, 9829905) although in some of these individuals another variant was identified in the same allele. ClinVar contains an entry for this variant (Variation ID: 370151). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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