NM_000053.4(ATP7B):c.3550A>G (p.Ile1184Val) AND Wilson disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 13, 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:: RCV002521469.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.3550A>G (p.Ile1184Val)]

NM_000053.4(ATP7B):c.3550A>G (p.Ile1184Val)

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.3550A>G (p.Ile1184Val)

HGVS:

NC_000013.11:g.51941087T>C
NG_008806.1:g.75408A>G
NM_000053.4:c.3550A>GMANE SELECT
NM_001005918.3:c.2929A>G
NM_001243182.2:c.3217A>G
NM_001330578.2:c.3316A>G
NM_001330579.2:c.3298A>G
NP_000044.2:p.Ile1184Val
NP_001005918.1:p.Ile977Val
NP_001230111.1:p.Ile1073Val
NP_001317507.1:p.Ile1106Val
NP_001317508.1:p.Ile1100Val
NC_000013.10:g.52515223T>C

Protein change:

I1073V

Links:

dbSNP: rs1057519121

NCBI 1000 Genomes Browser:

rs1057519121

Molecular consequence:

NM_000053.4:c.3550A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2929A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.3217A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.3316A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.3298A>G - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003486146	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23518715, 25678388, 32770663, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003486146

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2022)

germline

clinical testing

PubMed (4)
[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

A genetic study of Wilson's disease in the United Kingdom.

Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, Klaffke S, Joyce CJ, Dhawan A, Hadzic N, Mieli-Vergani G, Kirk R, Elizabeth Allen K, Nicholl D, Wong S, Griffiths W, Smithson S, Giffin N, Taha A, Connolly S, Gillett GT, Tanner S, et al.

Brain. 2013 May;136(Pt 5):1476-87. doi: 10.1093/brain/awt035. Epub 2013 Mar 21.

PubMed [citation]

PMID:: 23518715
PMCID:: PMC3634195

Hepatic steatosis in Wilson disease--Role of copper and PNPLA3 mutations.

Stättermayer AF, Traussnigg S, Dienes HP, Aigner E, Stauber R, Lackner K, Hofer H, Stift J, Wrba F, Stadlmayr A, Datz C, Strasser M, Maieron A, Trauner M, Ferenci P.

J Hepatol. 2015 Jul;63(1):156-63. doi: 10.1016/j.jhep.2015.01.034. Epub 2015 Feb 9.

PubMed [citation]

PMID:: 25678388

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003486146.1

#	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 isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1184 of the ATP7B protein (p.Ile1184Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 374482). 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. This variant disrupts the p.Ile1184 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23518715, 25678388, 32770663). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine