NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 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:: RCV001388601.9

Allele description [Variation Report for NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln)]

NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln)

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.3641G>A (p.Arg1214Gln)

Other names:

p.Arg1214Gln; NM_000352.6(ABCC8):c.3641G>A

HGVS:

NC_000011.10:g.17402670C>T
NG_008867.1:g.79233G>A
NM_000352.6:c.3641G>AMANE SELECT
NM_001287174.3:c.3644G>A
NM_001351295.2:c.3707G>A
NM_001351296.2:c.3641G>A
NM_001351297.2:c.3638G>A
NP_000343.2:p.Arg1214Gln
NP_001274103.1:p.Arg1215Gln
NP_001338224.1:p.Arg1236Gln
NP_001338225.1:p.Arg1214Gln
NP_001338226.1:p.Arg1213Gln
LRG_790t1:c.3641G>A
LRG_790t2:c.3644G>A
LRG_790:g.79233G>A
LRG_790p1:p.Arg1214Gln
LRG_790p2:p.Arg1215Gln
NC_000011.9:g.17424217C>T
NM_000352.3:c.3641G>A
NM_000352.5:c.3641G>A
NR_147094.2:n.3790G>A

Protein change:

R1213Q

Links:

dbSNP: rs367850779

NCBI 1000 Genomes Browser:

rs367850779

Molecular consequence:

NM_000352.6:c.3641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3644G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3707G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3638G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3790G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589657	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 15562009, 20685672, 9648840, 17575084, 23275527, 24401662, 24937539, 26180531, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589657

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2023)

germline

clinical testing

PubMed (9)
[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 correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.

Henwood MJ, Kelly A, Macmullen C, Bhatia P, Ganguly A, Thornton PS, Stanley CA.

J Clin Endocrinol Metab. 2005 Feb;90(2):789-94. Epub 2004 Nov 23.

PubMed [citation]

PMID:: 15562009

ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

Bellanné-Chantelot C, Saint-Martin C, Ribeiro MJ, Vaury C, Verkarre V, Arnoux JB, Valayannopoulos V, Gobrecht S, Sempoux C, Rahier J, Fournet JC, Jaubert F, Aigrain Y, Nihoul-Fékété C, de Lonlay P.

J Med Genet. 2010 Nov;47(11):752-9. doi: 10.1136/jmg.2009.075416. Epub 2010 Aug 3.

PubMed [citation]

PMID:: 20685672

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589657.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1214 of the ABCC8 protein (p.Arg1214Gln). This variant is present in population databases (rs367850779, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive familial hyperinsulinism (PMID: 15562009, 20685672). This variant is also known as R1215Q. ClinVar contains an entry for this variant (Variation ID: 632619). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 9648840). This variant disrupts the p.Arg1214 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17575084, 23275527, 24401662, 24937539, 26180531). 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: Dec 14, 2024

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