ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2297C>G (p.Thr766Arg) (rs121907997)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000004065 SCV000626840 pathogenic Wilson disease 2017-08-09 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 766 of the ATP7B protein (p.Thr766Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (rs121907997, ExAC no frequency). This variant has been reported as homozygous or in combination with another pathogenic ATP7B variant in individuals affected with Wilson disease (PMID: 15557537, 21956287). In addition, this variant has been observed to segregate with Wilson disease in a family where it was observed on the opposite chromosome (in trans) from a pathogenic variant in ATP7B (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 3861). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004065 SCV000024231 pathogenic Wilson disease 2004-11-23 no assertion criteria provided literature only

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