Submissions for variant NM_000053.4(ATP7B):c.1924G>C (p.Asp642His)

dbSNP: rs72552285

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169521	SCV000220995	likely pathogenic	Wilson disease	2014-12-29	criteria provided, single submitter	literature only
Invitae	RCV000169521	SCV000626833	pathogenic	Wilson disease	2023-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 642 of the ATP7B protein (p.Asp642His). This variant is present in population databases (rs72552285, gnomAD 0.006%). This missense change has been observed in individual(s) with Wilson syndrome and a copper metabolism disorder and Wilson disease (PMID: 18483695, 21610751, 21682854, 22308153, 24706876, 29540233; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189109). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7B protein function. Experimental studies have shown that this missense change does not substantially affect ATP7B function (PMID: 18203200). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV001508348	SCV001714453	likely pathogenic	not provided	2020-08-26	criteria provided, single submitter	clinical testing	PS4_moderate, PM2, PM3, PP3, PP4
Genome-Nilou Lab	RCV000169521	SCV001810287	likely pathogenic	Wilson disease	2021-07-22	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000169521	SCV002024426	likely pathogenic	Wilson disease	2021-05-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000169521	SCV002813833	likely pathogenic	Wilson disease	2021-12-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000169521	SCV004216321	pathogenic	Wilson disease	2023-09-26	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000169521	SCV004805055	pathogenic	Wilson disease	2024-03-17	criteria provided, single submitter	research
Natera, Inc.	RCV000169521	SCV002087859	likely pathogenic	Wilson disease	2021-04-02	no assertion criteria provided	clinical testing