NM_001374385.1(ATP8B1):c.1982T>C (p.Ile661Thr) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Feb 6, 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:: RCV000723736.14

Allele description [Variation Report for NM_001374385.1(ATP8B1):c.1982T>C (p.Ile661Thr)]

NM_001374385.1(ATP8B1):c.1982T>C (p.Ile661Thr)

Gene:

ATP8B1:ATPase phospholipid transporting 8B1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.31

Genomic location:

Preferred name:

NM_001374385.1(ATP8B1):c.1982T>C (p.Ile661Thr)

HGVS:

NC_000018.10:g.57669433A>G
NG_007148.3:g.139390T>C
NM_001374385.1:c.1982T>CMANE SELECT
NM_001374386.1:c.1832T>C
NM_005603.6:c.1982T>C
NP_001361314.1:p.Ile661Thr
NP_001361315.1:p.Ile611Thr
NP_005594.1:p.Ile661Thr
NP_005594.2:p.Ile661Thr
LRG_1205t1:c.1982T>C
LRG_1205:g.139390T>C
LRG_1205p1:p.Ile661Thr
NC_000018.9:g.55336665A>G
NM_005603.4:c.1982T>C
NM_005603.5:c.1982T>C
O43520:p.Ile661Thr

Protein change:

I611T; ILE661THR

Links:

UniProtKB: O43520#VAR_008812; OMIM: 602397.0006; dbSNP: rs121909100

NCBI 1000 Genomes Browser:

rs121909100

Molecular consequence:

NM_001374385.1:c.1982T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374386.1:c.1832T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005603.6:c.1982T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000331489	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jun 3, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19731236, 19918981, 9500542, 9918928 Citation Link,
SCV001741583	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001929768	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002022083	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 3, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004242942	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004265336	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 9500542, 9918928, 15239083, 20232290, 33666275, 34016879, 19731236, 19918981, 28492532

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis.

Bull LN, van Eijk MJ, Pawlikowska L, DeYoung JA, Juijn JA, Liao M, Klomp LW, Lomri N, Berger R, Scharschmidt BF, Knisely AS, Houwen RH, Freimer NB.

Nat Genet. 1998 Mar;18(3):219-24.

PubMed [citation]

PMID:: 9500542

See all PubMed Citations (10)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000331489.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

#	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		3	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001741583.3

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001929768.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002022083.3

#	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 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004242942.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004265336.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 661 of the ATP8B1 protein (p.Ile661Thr). This variant is present in population databases (rs121909100, gnomAD 0.02%). This missense change has been observed in individuals with benign recurrent intrahepatic cholestasis and/or progressive familial intrahepatic cholestasis (PMID: 9500542, 9918928, 15239083, 20232290, 33666275, 34016879). ClinVar contains an entry for this variant (Variation ID: 7267). 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 ATP8B1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ATP8B1 function (PMID: 19731236, 19918981). 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

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine