NM_000053.4(ATP7B):c.2663C>T (p.Thr888Ile) AND Wilson disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 5, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003111991.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.2663C>T (p.Thr888Ile)]

NM_000053.4(ATP7B):c.2663C>T (p.Thr888Ile)

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.2663C>T (p.Thr888Ile)

HGVS:

NC_000013.11:g.51950074G>A
NG_008806.1:g.66421C>T
NM_000053.4:c.2663C>TMANE SELECT
NM_001005918.3:c.2177C>T
NM_001243182.2:c.2330C>T
NM_001330578.2:c.2429C>T
NM_001330579.2:c.2411C>T
NM_001406511.1:c.2663C>T
NM_001406512.1:c.2663C>T
NM_001406513.1:c.2663C>T
NM_001406514.1:c.2630C>T
NM_001406515.1:c.2663C>T
NM_001406516.1:c.2663C>T
NM_001406517.1:c.2567C>T
NM_001406518.1:c.2567C>T
NM_001406519.1:c.2663C>T
NM_001406520.1:c.2519C>T
NM_001406521.1:c.2519C>T
NM_001406522.1:c.2519C>T
NM_001406523.1:c.2663C>T
NM_001406524.1:c.2486C>T
NM_001406525.1:c.2663C>T
NM_001406526.1:c.2663C>T
NM_001406527.1:c.2429C>T
NM_001406528.1:c.2429C>T
NM_001406530.1:c.2423C>T
NM_001406531.1:c.2411C>T
NM_001406532.1:c.2411C>T
NM_001406534.1:c.2429C>T
NM_001406535.1:c.2663C>T
NM_001406536.1:c.2333C>T
NM_001406537.1:c.2519C>T
NM_001406538.1:c.2429C>T
NM_001406539.1:c.2234C>T
NM_001406540.1:c.2411C>T
NM_001406541.1:c.2177C>T
NM_001406542.1:c.2177C>T
NM_001406543.1:c.2315C>T
NM_001406544.1:c.2081C>T
NM_001406545.1:c.2015C>T
NM_001406546.1:c.2177C>T
NM_001406547.1:c.2015C>T
NM_001406548.1:c.1373C>T
NP_000044.2:p.Thr888Ile
NP_001005918.1:p.Thr726Ile
NP_001230111.1:p.Thr777Ile
NP_001317507.1:p.Thr810Ile
NP_001317508.1:p.Thr804Ile
NP_001393440.1:p.Thr888Ile
NP_001393441.1:p.Thr888Ile
NP_001393442.1:p.Thr888Ile
NP_001393443.1:p.Thr877Ile
NP_001393444.1:p.Thr888Ile
NP_001393445.1:p.Thr888Ile
NP_001393446.1:p.Thr856Ile
NP_001393447.1:p.Thr856Ile
NP_001393448.1:p.Thr888Ile
NP_001393449.1:p.Thr840Ile
NP_001393450.1:p.Thr840Ile
NP_001393451.1:p.Thr840Ile
NP_001393452.1:p.Thr888Ile
NP_001393453.1:p.Thr829Ile
NP_001393454.1:p.Thr888Ile
NP_001393455.1:p.Thr888Ile
NP_001393456.1:p.Thr810Ile
NP_001393457.1:p.Thr810Ile
NP_001393459.1:p.Thr808Ile
NP_001393460.1:p.Thr804Ile
NP_001393461.1:p.Thr804Ile
NP_001393463.1:p.Thr810Ile
NP_001393464.1:p.Thr888Ile
NP_001393465.1:p.Thr778Ile
NP_001393466.1:p.Thr840Ile
NP_001393467.1:p.Thr810Ile
NP_001393468.1:p.Thr745Ile
NP_001393469.1:p.Thr804Ile
NP_001393470.1:p.Thr726Ile
NP_001393471.1:p.Thr726Ile
NP_001393472.1:p.Thr772Ile
NP_001393473.1:p.Thr694Ile
NP_001393474.1:p.Thr672Ile
NP_001393475.1:p.Thr726Ile
NP_001393476.1:p.Thr672Ile
NP_001393477.1:p.Thr458Ile
NC_000013.10:g.52524210G>A

Protein change:

T458I

Molecular consequence:

NM_000053.4:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2330C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.2429C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.2411C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406511.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406512.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406513.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406514.1:c.2630C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406515.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406516.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406517.1:c.2567C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406518.1:c.2567C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406519.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406520.1:c.2519C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406521.1:c.2519C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406522.1:c.2519C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406523.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406524.1:c.2486C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406525.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406526.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406527.1:c.2429C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406528.1:c.2429C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406530.1:c.2423C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406531.1:c.2411C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406532.1:c.2411C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406534.1:c.2429C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406535.1:c.2663C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406536.1:c.2333C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406537.1:c.2519C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406538.1:c.2429C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406539.1:c.2234C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406540.1:c.2411C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406541.1:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406542.1:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406543.1:c.2315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406544.1:c.2081C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406545.1:c.2015C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406546.1:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406547.1:c.2015C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406548.1:c.1373C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Wilson disease (WND)
Synonyms:: Wilson's disease; Hepatolenticular degeneration
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
SCV003784694	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 5, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23843956, 27398169, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003784694

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 5, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Novel ATPase Cu(2+) transporting beta polypeptide mutations in Chinese families with Wilson's disease.

Gu S, Yang H, Qi Y, Deng X, Zhang L, Guo Y, Huang Q, Li J, Shi X, Song Z, Deng H.

PLoS One. 2013 Jul 2;8(7):e66526. doi: 10.1371/journal.pone.0066526. Print 2013.

PubMed [citation]

PMID:: 23843956
PMCID:: PMC3699604

Mutational analysis of ATP7B in Chinese Wilson disease patients.

Hua R, Hua F, Jiao Y, Pan Y, Yang X, Peng S, Niu J.

Am J Transl Res. 2016;8(6):2851-61.

PubMed [citation]

PMID:: 27398169
PMCID:: PMC4931180

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003784694.2

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 888 of the ATP7B protein (p.Thr888Ile). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. 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. This variant disrupts the p.Thr888 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23843956, 27398169). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

Last Updated: Nov 11, 2023

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