NM_000352.6(ABCC8):c.4135C>T (p.Arg1379Cys) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 24, 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:: RCV001851773.9

Allele description [Variation Report for NM_000352.6(ABCC8):c.4135C>T (p.Arg1379Cys)]

NM_000352.6(ABCC8):c.4135C>T (p.Arg1379Cys)

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.4135C>T (p.Arg1379Cys)

HGVS:

NC_000011.10:g.17395915G>A
NG_008867.1:g.85988C>T
NM_000352.4(ABCC8):c.4135C>T
NM_000352.6:c.4135C>TMANE SELECT
NM_001287174.3:c.4138C>T
NM_001351295.2:c.4201C>T
NM_001351296.2:c.4135C>T
NM_001351297.2:c.4132C>T
NP_000343.2:p.Arg1379Cys
NP_001274103.1:p.Arg1380Cys
NP_001338224.1:p.Arg1401Cys
NP_001338225.1:p.Arg1379Cys
NP_001338226.1:p.Arg1378Cys
LRG_790t1:c.4135C>T
LRG_790t2:c.4138C>T
LRG_790:g.85988C>T
LRG_790p1:p.Arg1379Cys
LRG_790p2:p.Arg1380Cys
NC_000011.9:g.17417462G>A
NC_000011.9:g.17417462G>A
NM_000352.4(ABCC8):c.4135C>T
NM_000352.4:c.4135C>T
NR_147094.2:n.4430C>T
p.Arg1379Cys

Protein change:

R1378C; ARG1379CYS

Links:

OMIM: 600509.0019; dbSNP: rs137852673

NCBI 1000 Genomes Browser:

rs137852673

Molecular consequence:

NM_000352.6:c.4135C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.4138C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.4201C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.4135C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.4132C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.4430C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002181676	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 24, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18025464, 16885549, 17446535, 27681997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002181676

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 24, 2022)

germline

clinical testing

PubMed (5)
[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

Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.

de Wet H, Rees MG, Shimomura K, Aittoniemi J, Patch AM, Flanagan SE, Ellard S, Hattersley AT, Sansom MS, Ashcroft FM.

Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18988-92. Epub 2007 Nov 19.

PubMed [citation]

PMID:: 18025464
PMCID:: PMC2141895

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002181676.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1379 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been observed in individuals with ABCC8-related conditions (PMID: 17446535), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 18025464). 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: 9105). This variant is also known as R1380C. This missense change has been observed in individuals with autosomal dominant ABCC8-related early onset diabetes (PMID: 16885549, 17446535, 27681997). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1379 of the ABCC8 protein (p.Arg1379Cys).

#	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 13, 2024

ClinVar

Relating variation to medicine