NM_000352.6(ABCC8):c.4132G>C (p.Gly1378Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000710385.5

Allele description [Variation Report for NM_000352.6(ABCC8):c.4132G>C (p.Gly1378Arg)]

NM_000352.6(ABCC8):c.4132G>C (p.Gly1378Arg)

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.4132G>C (p.Gly1378Arg)

HGVS:

NC_000011.10:g.17395918C>G
NG_008867.1:g.85985G>C
NM_000352.6:c.4132G>CMANE SELECT
NM_001287174.3:c.4135G>C
NM_001351295.2:c.4198G>C
NM_001351296.2:c.4132G>C
NM_001351297.2:c.4129G>C
NP_000343.2:p.Gly1378Arg
NP_001274103.1:p.Gly1379Arg
NP_001338224.1:p.Gly1400Arg
NP_001338225.1:p.Gly1378Arg
NP_001338226.1:p.Gly1377Arg
LRG_790t1:c.4132G>C
LRG_790t2:c.4135G>C
LRG_790:g.85985G>C
LRG_790p1:p.Gly1378Arg
LRG_790p2:p.Gly1379Arg
NC_000011.9:g.17417465C>G
NM_000352.3:c.4132G>C
NR_147094.2:n.4427G>C

Protein change:

G1377R

Links:

dbSNP: rs925231098

NCBI 1000 Genomes Browser:

rs925231098

Molecular consequence:

NM_000352.6:c.4132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.4135G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.4198G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.4132G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.4129G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.4427G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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gi|73695403|gb|BC103509.1|

Nucleotide
Profile neighbors for GEO Profiles (Select 69884200) (200)
GEO Profiles
Transcription factor-induced pluripotent stem cells
Transcription factor-induced pluripotent stem cells
Accession: GDS3842

GEO DataSets
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GEO DataSets
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gi|119121244|gnl|dbEST|43386198|dbj 6153.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000840595	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Mar 9, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23275527, 16357843, 9618169, 26467025
SCV003439708	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16357843, 23275527, 34304300, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000840595

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Mar 9, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003439708

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2023)

germline

clinical testing

PubMed (4)
[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

Genetic heterogeneity in familial hyperinsulinism.

Nestorowicz A, Glaser B, Wilson BA, Shyng SL, Nichols CG, Stanley CA, Thornton PS, Permutt MA.

Hum Mol Genet. 1998 Jul;7(7):1119-28. Erratum in: Hum Mol Genet 1998 Sep;7(9):1527.

PubMed [citation]

PMID:: 9618169

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (6)

Details of each submission

From Athena Diagnostics, SCV000840595.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439708.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1378 of the ABCC8 protein (p.Gly1378Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive familial hyperinsulinism (PMID: 16357843, 23275527). This variant is also known as p.Gly1379Arg. ClinVar contains an entry for this variant (Variation ID: 554195). 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%. This variant disrupts the p.Gly1378 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 34304300). 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: Sep 29, 2024

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