NM_000352.6(ABCC8):c.1969C>T (p.Arg657Trp) AND Leucine-induced hypoglycemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 11, 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:: RCV004784040.1

Allele description [Variation Report for NM_000352.6(ABCC8):c.1969C>T (p.Arg657Trp)]

NM_000352.6(ABCC8):c.1969C>T (p.Arg657Trp)

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.1969C>T (p.Arg657Trp)

HGVS:

NC_000011.10:g.17428360G>A
NG_008867.1:g.53543C>T
NM_000352.6:c.1969C>TMANE SELECT
NM_001287174.3:c.1969C>T
NM_001351295.2:c.2035C>T
NM_001351296.2:c.1966C>T
NM_001351297.2:c.1966C>T
NP_000343.2:p.Arg657Trp
NP_001274103.1:p.Arg657Trp
NP_001338224.1:p.Arg679Trp
NP_001338225.1:p.Arg656Trp
NP_001338226.1:p.Arg656Trp
LRG_790t1:c.1969C>T
LRG_790t2:c.1969C>T
LRG_790:g.53543C>T
LRG_790p1:p.Arg657Trp
LRG_790p2:p.Arg657Trp
NC_000011.9:g.17449907G>A
NM_000352.5:c.1969C>T
NR_147094.2:n.2035C>T

Protein change:

R656W

Links:

dbSNP: rs778117119

NCBI 1000 Genomes Browser:

rs778117119

Molecular consequence:

NM_000352.6:c.1969C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.1969C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.2035C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.1966C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.1966C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.2035C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Leucine-induced hypoglycemia (LIH)
Synonyms:: Leucine-sensitive hypoglycemia of infancy; Familial infantile hypoglycemia precipitated by leucine
Identifiers:: MONDO: MONDO:0009415; MedGen: C0271714; OMIM: 240800

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
SCV005397198	Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 11, 2022)	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

SCV005397198

Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 11, 2022)

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 Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center, SCV005397198.1

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

Description

This sequence variant is a single nucleotide substitution (C>T) at coding position 1969 of the ABCC8 gene that results in an arginine to tryptophan amino acid change at residue 657 of the ABCC8 protein. This is a previously reported variant (ClinVar) that has not been observed in individuals with ABCC8-related illness in the literature, to our knowledge. This variant is present in the gnomAD population database (8 of 251000 alleles or 0.003%). Multiple bioinformatic tools predict that this variant would be tolerated, and the Arg657 residue is not well conserved among the primate species examined. Functiol studies testing the effect of this variant have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this to be a variant of uncertain significance. ACMG Criteria: BP4, PM2

#	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: Nov 18, 2024

ClinVar

Relating variation to medicine