NM_000352.6(ABCC8):c.4258C>T (p.Arg1420Cys) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 2023
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:: RCV001235181.7

Allele description

NM_000352.6(ABCC8):c.4258C>T (p.Arg1420Cys)

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.4258C>T (p.Arg1420Cys)

HGVS:

NC_000011.10:g.17395659G>A
NG_008867.1:g.86244C>T
NM_000352.6:c.4258C>TMANE SELECT
NM_001287174.3:c.4261C>T
NM_001351295.2:c.4324C>T
NM_001351296.2:c.4258C>T
NM_001351297.2:c.4255C>T
NP_000343.2:p.Arg1420Cys
NP_001274103.1:p.Arg1421Cys
NP_001338224.1:p.Arg1442Cys
NP_001338225.1:p.Arg1420Cys
NP_001338226.1:p.Arg1419Cys
LRG_790t1:c.4258C>T
LRG_790t2:c.4261C>T
LRG_790:g.86244C>T
LRG_790p1:p.Arg1420Cys
LRG_790p2:p.Arg1421Cys
NC_000011.9:g.17417206G>A
NM_000352.3:c.4258C>T
NM_000352.4:c.4258C>T
NM_001287174.1:c.4261C>T
NR_147094.2:n.4553C>T

Protein change:

R1419C; ARG1421CYS

Links:

OMIM: 600509.0009; dbSNP: rs28938469

NCBI 1000 Genomes Browser:

rs28938469

Molecular consequence:

NM_000352.6:c.4258C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.4261C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.4324C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.4258C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.4255C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.4553C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001407856	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10993895, 26246406, 9769320, 10615958, 17378627, 32041611, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001407856

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2023)

germline

clinical testing

PubMed (7)
[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

Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy.

Matsuo M, Trapp S, Tanizawa Y, Kioka N, Amachi T, Oka Y, Ashcroft FM, Ueda K.

J Biol Chem. 2000 Dec 29;275(52):41184-91.

PubMed [citation]

PMID:: 10993895

ABCC8 R1420H Loss-of-Function Variant in a Southwest American Indian Community: Association With Increased Birth Weight and Doubled Risk of Type 2 Diabetes.

Baier LJ, Muller YL, Remedi MS, Traurig M, Piaggi P, Wiessner G, Huang K, Stacy A, Kobes S, Krakoff J, Bennett PH, Nelson RG, Knowler WC, Hanson RL, Nichols CG, Bogardus C.

Diabetes. 2015 Dec;64(12):4322-32. doi: 10.2337/db15-0459. Epub 2015 Aug 5.

PubMed [citation]

PMID:: 26246406
PMCID:: PMC4657583

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001407856.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1420 of the ABCC8 protein (p.Arg1420Cys). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 10615958, 10993895, 26246406). 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 ABCC8 protein function. ClinVar contains an entry for this variant (Variation ID: 9095). This variant is also known as p.Arg1421Cys. This missense change has been observed in individuals with clinical features of dyslipidemia and/or familial hyperinsulinemia (PMID: 9769320, 10615958, 17378627, 32041611).

#	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: Sep 16, 2024

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