NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV002517038.5

Allele description [Variation Report for NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)]

NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)

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.3544C>T (p.Arg1182Trp)

HGVS:

NC_000011.10:g.17404525G>A
NG_008867.1:g.77378C>T
NM_000352.6:c.3544C>TMANE SELECT
NM_001287174.3:c.3547C>T
NM_001351295.2:c.3610C>T
NM_001351296.2:c.3544C>T
NM_001351297.2:c.3541C>T
NP_000343.2:p.Arg1182Trp
NP_001274103.1:p.Arg1183Trp
NP_001338224.1:p.Arg1204Trp
NP_001338225.1:p.Arg1182Trp
NP_001338226.1:p.Arg1181Trp
LRG_790t1:c.3544C>T
LRG_790t2:c.3547C>T
LRG_790:g.77378C>T
LRG_790p1:p.Arg1182Trp
LRG_790p2:p.Arg1183Trp
NC_000011.9:g.17426072G>A
NM_000352.3:c.3544C>T
NR_147094.2:n.3693C>T

Protein change:

R1181W

Links:

dbSNP: rs797045209

NCBI 1000 Genomes Browser:

rs797045209

Molecular consequence:

NM_000352.6:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3610C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3541C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3693C>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
SCV003522326	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 32893419, 16885549, 17446535, 22749773, 24622368, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003522326

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2023)

germline

clinical testing

PubMed (6)
[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

Genotype-phenotype correlation of K(ATP) channel gene defects causing permanent neonatal diabetes in Indian patients.

Gopi S, Kavitha B, Kanthimathi S, Kannan A, Kumar R, Joshi R, Kanodia S, Arya AD, Pendsey S, Pendsey S, Raghupathy P, Mohan V, Radha V.

Pediatr Diabetes. 2021 Feb;22(1):82-92. doi: 10.1111/pedi.13109. Epub 2020 Sep 15.

PubMed [citation]

PMID:: 32893419

Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.

Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P.

N Engl J Med. 2006 Aug 3;355(5):456-66.

PubMed [citation]

PMID:: 16885549

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003522326.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1182 of the ABCC8 protein (p.Arg1182Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant neonatal diabetes mellitus (PMID: 17446535, 32893419). In at least one individual the variant was observed to be de novo. This variant is also known as R1183W. ClinVar contains an entry for this variant (Variation ID: 210076). 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. This variant disrupts the p.Arg1182 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16885549, 17446535, 22749773, 24622368). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024

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