ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3659C>T (p.Thr1220Met) (rs193922107)

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Total submissions: 5
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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 RCV000029374 SCV000052022 pathogenic Wilson disease 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Counsyl RCV000029374 SCV000220459 likely pathogenic Wilson disease 2014-06-29 criteria provided, single submitter literature only
GeneDx RCV000413521 SCV000491163 pathogenic not provided 2020-09-09 criteria provided, single submitter clinical testing Published functional studies demonstrate that site-directed mutagenesis of the residues in the ATP-binding domain found that alteration of this sequence abolishes calcium transport activity (Loudianos et al. 1996); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16283883, 17949296, 22763723, 20931554, 25497208, 24661374, 30275481, 22692182, 21610751, 23774950, 8931691, 31708252, 31400605)
Fulgent Genetics,Fulgent Genetics RCV000029374 SCV000611172 likely pathogenic Wilson disease 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000029374 SCV000940902 pathogenic Wilson disease 2020-09-19 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1220 of the ATP7B protein (p.Thr1220Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 25497208, 22763723, 21610751, 24661374, Invitae). ClinVar contains an entry for this variant (Variation ID: 35725). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.

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