NM_000352.6(ABCC8):c.4136G>T (p.Arg1379Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 16, 2019
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:: RCV001818180.4

Allele description [Variation Report for NM_000352.6(ABCC8):c.4136G>T (p.Arg1379Leu)]

NM_000352.6(ABCC8):c.4136G>T (p.Arg1379Leu)

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.4136G>T (p.Arg1379Leu)

HGVS:

NC_000011.10:g.17395914C>A
NG_008867.1:g.85989G>T
NM_000352.6:c.4136G>TMANE SELECT
NM_001287174.3:c.4139G>T
NM_001351295.2:c.4202G>T
NM_001351296.2:c.4136G>T
NM_001351297.2:c.4133G>T
NP_000343.2:p.Arg1379Leu
NP_001274103.1:p.Arg1380Leu
NP_001338224.1:p.Arg1401Leu
NP_001338225.1:p.Arg1379Leu
NP_001338226.1:p.Arg1378Leu
LRG_790t1:c.4136G>T
LRG_790t2:c.4139G>T
LRG_790:g.85989G>T
LRG_790p1:p.Arg1379Leu
LRG_790p2:p.Arg1380Leu
NC_000011.9:g.17417461C>A
NM_000352.3:c.4136G>T
NM_000352.4:c.4136G>T
NR_147094.2:n.4431G>T

Protein change:

R1378L

Links:

dbSNP: rs193922401

NCBI 1000 Genomes Browser:

rs193922401

Molecular consequence:

NM_000352.6:c.4136G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.4139G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.4202G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.4136G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.4133G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.4431G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Homo sapiens mucin (MUC3) mRNA, partial cds
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002067352	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 16, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002067352

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 16, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002067352.1

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

Description

DNA sequence analysis of the ABCC8 gene demonstrated a sequence change, c.4136G>T, in exon 34 that results in an amino acid change, p.Arg1379Leu. The p.Arg1379Leu change has been identified in patients with transient neonatal diabetes and family members of these individuals who were diagnosed with diabetes in adulthood (PMID: 18025464). Additionally, several other mutations affecting the same amino acid residue (p.Arg1379Cys, p.Arg1379His, p.Arg1379Pro, p.Arg1379Ser) have been reported in patients with neonatal diabetes as well as adult onset diabetes (PMIDs: 18025464, 16885549, 24622368, 25555642). The p.Arg1379Leu change is absent from large population databases such as ExAC and gnomAD. The p.Arg1379Leu change affects a highly conserved amino acid residue located in a domain of the SUR1 protein that is known to be functional. The p.Arg1379Leu substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL).

#	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

Last Updated: Apr 9, 2023

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