NM_000352.6(ABCC8):c.4135C>T (p.Arg1379Cys) AND Transient neonatal diabetes mellitus 2

Clinical significance:Pathogenic (Last evaluated: Nov 27, 2007)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000009673.4

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
  • 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)

Name:
Transient neonatal diabetes mellitus 2 (TNDM2)
Identifiers:
MONDO: MONDO:0012480; MedGen: C1835887; Orphanet: 99886; OMIM: 610374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029891OMIMno assertion criteria providedPathogenic
(Nov 27, 2007)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

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

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

Details of each submission

From OMIM, SCV000029891.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a French girl (family 19) with transient neonatal diabetes mellitus (TNDM2; 610374) who had a recurrence of diabetes at age 6 and in affected members of an unrelated 5-generation French family (family 17) with transient neonatal diabetes and adult-onset type II diabetes mellitus (125853), Babenko et al. (2006) identified heterozygosity for an arg1379-to-cys (R1379C) substitution. The mutation arose de novo in the first patient. The 5-year-old female proband of the family had transient neonatal diabetes. Her father developed diabetes at age 32 that was treated with sulfonylureas, and her paternal grandmother was diagnosed with gestational diabetes and treated with diet, and a paternal great-aunt was diagnosed at age 44 with diabetes that was also treated with sulfonylureas. Babenko et al. (2006) proposed that mutations of the ABCC8 gene might give rise to a monogenic form of type II diabetes with variable expression and age at onset.

De Wet et al. (2007) performed functional studies of this mutation, which they designated R1380C, and demonstrated enhanced MgATP hydrolysis by purified isolated fusion proteins of maltose-binding protein and the second nucleotide-binding domain of ABCC8, in which the mutation is located. This increase in ATPase activity reduced the sensitivity of the channel to inhibition by MgATP and increased the whole-cell K(ATP) current. The authors noted that in pancreatic beta cells, such an increase in K(ATP) current would be expected to impair insulin secretion and thereby cause diabetes.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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