NM_000053.4(ATP7B):c.2549C>T (p.Thr850Ile) AND Wilson disease

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Apr 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000670079.14

Allele description [Variation Report for NM_000053.4(ATP7B):c.2549C>T (p.Thr850Ile)]

NM_000053.4(ATP7B):c.2549C>T (p.Thr850Ile)

Gene:

ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.2549C>T (p.Thr850Ile)

HGVS:

NC_000013.11:g.51950298G>A
NG_008806.1:g.66197C>T
NM_000053.4:c.2549C>TMANE SELECT
NM_001005918.3:c.2063C>T
NM_001243182.2:c.2216C>T
NM_001330578.2:c.2315C>T
NM_001330579.2:c.2297C>T
NP_000044.2:p.Thr850Ile
NP_001005918.1:p.Thr688Ile
NP_001230111.1:p.Thr739Ile
NP_001317507.1:p.Thr772Ile
NP_001317508.1:p.Thr766Ile
NC_000013.10:g.52524434G>A
NM_000053.3:c.2549C>T
p.Thr850Ile

Protein change:

T688I

Links:

dbSNP: rs777629392

NCBI 1000 Genomes Browser:

rs777629392

Molecular consequence:

NM_000053.4:c.2549C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2063C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.2315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.2297C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Wilson disease (WND)
Synonyms:: Wilson's disease
Identifiers:: MONDO: MONDO:0010200; MedGen: C0019202; Orphanet: 905; OMIM: 277900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000794895	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Oct 18, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25089800, 27398169, 21034864 Citation Link,
SCV001201648	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21034864, 27398169, 29321352, 28492532
SCV002087843	Natera, Inc.	no assertion criteria provided	Pathogenic (Jun 28, 2021)	germline	clinical testing
SCV002799405	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004216408	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 25, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational characterization of ATP7B gene in 103 Wilson's disease patients from Southern China: identification of three novel mutations.

Wei Z, Huang Y, Liu A, Diao S, Yu Q, Peng Z, Hong M.

Neuroreport. 2014 Oct 1;25(14):1075-80. doi: 10.1097/WNR.0000000000000216.

PubMed [citation]

PMID:: 25089800

Six novel ATP7B mutations in Thai patients with Wilson disease.

Panichareon B, Taweechue K, Thongnoppakhun W, Aksornworanart M, Pithukpakorn M, Yenchitsomanus PT, Limwongse C, Limjindaporn T.

Eur J Med Genet. 2011 Mar-Apr;54(2):103-7. doi: 10.1016/j.ejmg.2010.10.008. Epub 2010 Oct 27.

PubMed [citation]

PMID:: 21034864

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000794895.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001201648.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 850 of the ATP7B protein (p.Thr850Ile). This variant is present in population databases (rs777629392, gnomAD 0.01%). This missense change has been observed in individual(s) with Wilson disease (PMID: 21034864, 27398169, 29321352). ClinVar contains an entry for this variant (Variation ID: 554444). 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 expected to disrupt ATP7B protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002087843.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002799405.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004216408.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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