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NM_000053.4(ATP7B):c.3316G>A (p.Val1106Ile)

Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
5 (Most recent: Oct 12, 2021)
Last evaluated:
Aug 10, 2021
Variation ID:
single nucleotide variant

NM_000053.4(ATP7B):c.3316G>A (p.Val1106Ile)

Allele ID
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Genomic location
13: 51942482 (GRCh38) GRCh38 UCSC
13: 52516618 (GRCh37) GRCh37 UCSC
Nucleotide Protein Molecular
NM_000053.4:c.3316G>A MANE Select NP_000044.2:p.Val1106Ile missense
... more HGVS
Protein change
V1106I, V1028I, V995I, V1022I, V899I
Other names
Canonical SPDI
Functional consequence
Global minor allele frequency (GMAF)
0.00040 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00013
Trans-Omics for Precision Medicine (TOPMed) 0.00018
The Genome Aggregation Database (gnomAD), exomes 0.00012
The Genome Aggregation Database (gnomAD) 0.00016
1000 Genomes Project 0.00040
ClinGen: CA6988741
dbSNP: rs541208827

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Aug 10, 2021 RCV000674801.5
Uncertain significance 1 criteria provided, single submitter Jun 13, 2019 RCV000586649.2
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ATP7B - - GRCh38
1321 1385

Submitted interpretations and evidence

(Last evaluated)
Review status
(Assertion criteria)
Submitter Supporting information
Likely pathogenic
(May 25, 2018)
criteria provided, single submitter
Method: clinical testing
Wilson disease
Allele origin: unknown
Accession: SCV000800200.1
Submitted: (Jul 10, 2018)
Evidence details
PubMed (10)
Likely pathogenic
(Oct 05, 2018)
criteria provided, single submitter
Method: clinical testing
Wilson disease
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915634.1
Submitted: (Feb 01, 2019)
Evidence details
PubMed (12)
The ATP7B c.3316G>A (p.Val1106Ile) variant is a missense variant that has been widely reported in association with Wilson disease, primarily in individuals of Asian ancestry. … (more)
Uncertain significance
(Jun 13, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694444.2
Submitted: (Sep 24, 2019)
Evidence details
PubMed (22)
Variant summary: ATP7B c.3316G>A (p.Val1106Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
(Sep 10, 2020)
criteria provided, single submitter
Method: clinical testing
Wilson disease
Allele origin: germline
Accession: SCV001411757.2
Submitted: (Jan 07, 2021)
Evidence details
PubMed (5)
This sequence change replaces valine with isoleucine at codon 1106 of the ATP7B protein (p.Val1106Ile). The valine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Aug 10, 2021)
criteria provided, single submitter
Method: clinical testing
Wilson disease
Allele origin: germline
Nilou-Genome Lab
Accession: SCV001977133.1
Submitted: (Oct 12, 2021)
Evidence details

Functional evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Title Author Journal Year Link
Novel mutations found in the ATP7B gene in Chinese patients with Wilson's disease. Qian Z Molecular genetics & genomic medicine 2019 PMID: 30884209
Complex ATP7B mutation patterns in Wilson disease and evaluation of a yeast model for functional analysis of variants. Li X Human mutation 2019 PMID: 30702195
Multiplex Ligation-dependent Probe Amplification Analysis Subsequent to Direct DNA Full Sequencing for Identifying <i>ATP7B</i> Mutations and Phenotype Correlations in Children with Wilson Disease. Shim JO Journal of Korean medical science 2018 PMID: 29930488
Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease. Wang C Liver international : official journal of the International Association for the Study of the Liver 2018 PMID: 29637721
Carrier frequency of Wilson's disease in the Korean population: a DNA-based approach. Jang JH Journal of human genetics 2017 PMID: 28515472
Wilson's Disease in China. Xie JJ Neuroscience bulletin 2017 PMID: 28265897
Clinical features and outcome in patients with osseomuscular type of Wilson's disease. Yu H BMC neurology 2017 PMID: 28212618
Spectrum of ATP7B mutations and genotype-phenotype correlation in large-scale Chinese patients with Wilson Disease. Cheng N Clinical genetics 2017 PMID: 27982432
A special case of recurrent gross hematuria: Answers. Tu J Pediatric nephrology (Berlin, Germany) 2017 PMID: 26650869
Mutational analysis of ATP7B in Chinese Wilson disease patients. Hua R American journal of translational research 2016 PMID: 27398169
Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis. Dong Y Theranostics 2016 PMID: 27022412
Targeted next-generation sequencing of the ATP7B gene for molecular diagnosis of Wilson disease. Poon KS Clinical biochemistry 2016 PMID: 26483271
Analysis and application of ATP7B gene mutations in 35 patients with hepatolenticular degeneration. Zong YN Genetics and molecular research : GMR 2015 PMID: 26782526
Mutational characterization of ATP7B gene in 103 Wilson's disease patients from Southern China: identification of three novel mutations. Wei Z Neuroreport 2014 PMID: 25089800
Zinc mono-therapy in pre-symptomatic Chinese children with Wilson disease: a single center, retrospective study. Abuduxikuer K PloS one 2014 PMID: 24475083
Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation. Mukherjee S Parkinsonism & related disorders 2014 PMID: 24094725
A structural model of the copper ATPase ATP7B to facilitate analysis of Wilson disease-causing mutations and studies of the transport mechanism. Schushan M Metallomics : integrated biometal science 2012 PMID: 22692182
Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation. Wang LH Journal of human genetics 2011 PMID: 21796144
Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort. Lee BH Liver international : official journal of the International Association for the Study of the Liver 2011 PMID: 21645214
Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations. Li XH BMC medical genetics 2011 PMID: 21219664
Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease. Park S Human mutation 2007 PMID: 17587212
Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease. Liu XQ World journal of gastroenterology 2004 PMID: 14966923
Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease. Wu ZY Archives of neurology 2001 PMID: 11405812

Text-mined citations for rs541208827...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 30, 2021