NM_000053.4(ATP7B):c.2975C>T (p.Pro992Leu) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 19, 2017
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:: RCV002433726.2

Allele description [Variation Report for NM_000053.4(ATP7B):c.2975C>T (p.Pro992Leu)]

NM_000053.4(ATP7B):c.2975C>T (p.Pro992Leu)

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.2975C>T (p.Pro992Leu)

HGVS:

NC_000013.11:g.51946369G>A
NG_008806.1:g.70126C>T
NM_000053.4:c.2975C>TMANE SELECT
NM_001005918.3:c.2354C>T
NM_001243182.2:c.2642C>T
NM_001330578.2:c.2741C>T
NM_001330579.2:c.2723C>T
NP_000044.2:p.Pro992Leu
NP_001005918.1:p.Pro785Leu
NP_001230111.1:p.Pro881Leu
NP_001317507.1:p.Pro914Leu
NP_001317508.1:p.Pro908Leu
NC_000013.10:g.52520505G>A
NM_000053.2:c.2975C>T
NM_000053.3:c.2975C>T
P35670:p.Pro992Leu

Protein change:

P785L

Links:

UniProtKB: P35670#VAR_000749; dbSNP: rs201038679

NCBI 1000 Genomes Browser:

rs201038679

Molecular consequence:

NM_000053.4:c.2975C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2354C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.2741C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.2723C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002751167	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 19, 2017)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 11690702, 16649058, 16696937, 17717039, 18034201, 22240481, 23235335, 23843956, 9199563, 9671269, 9829905, 9837819 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002751167

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 19, 2017)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

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

High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis.

Caca K, Ferenci P, Kühn HJ, Polli C, Willgerodt H, Kunath B, Hermann W, Mössner J, Berr F.

J Hepatol. 2001 Nov;35(5):575-81.

PubMed [citation]

PMID:: 11690702

Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease.

Wu ZY, Zhao GX, Chen WJ, Wang N, Wan B, Lin MT, Murong SX, Yu L.

J Mol Med (Berl). 2006 May;84(5):438-42. Epub 2006 Jan 28.

PubMed [citation]

PMID:: 16649058

See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV002751167.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The p.P992L pathogenic mutation (also known as c.2975C>T), located in coding exon 13 of the ATP7B gene, results from a C to T substitution at nucleotide position 2975. The proline at codon 992 is replaced by leucine, an amino acid with similar properties. This mutation has been identified in multiple individuals with Wilson disease in the compound heterozygous or homozygous state (Nanji MS et al. Am. J. Hum. Genet., 1997 Jun;60:1423-9; Loudianos G et al. Hum. Mutat., 1998;12:89-94; Wu ZY et al. J. Mol. Med., 2006 May;84:438-42; Mak CM et al. J. Hum. Genet., 2008 Nov;53:55-63; Li K et al. J. Hum. Genet., 2013 Feb;58:67-72; Gu S et al. PLoS ONE, 2013 Jul;8:e66526). In addition, expression of this mutation in Sf9 cells showed partial copper uptake with normal phosphorylation activity (Huster D et al. Gastroenterology, 2012 Apr;142:947-956.e5). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Jun 17, 2024

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