ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2332C>G (p.Arg778Gly) (rs137853284)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000144367 SCV000220896 likely pathogenic Wilson disease 2014-11-20 criteria provided, single submitter literature only
Invitae RCV000144367 SCV000960064 pathogenic Wilson disease 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 778 of the ATP7B protein (p.Arg778Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 20517649, 21682854, 23333878). ClinVar contains an entry for this variant (Variation ID: 156283). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg778 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been observed in individuals with ATP7B-related conditions (PMID: 11243728, 11479773, 23518715, 17160357, 16998622), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000144367 SCV001149697 pathogenic Wilson disease 2019-01-23 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000144367 SCV000189434 not provided Wilson disease no assertion provided not provided

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