NM_000352.6(ABCC8):c.134C>T (p.Pro45Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 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:: RCV002512948.2

Allele description [Variation Report for NM_000352.6(ABCC8):c.134C>T (p.Pro45Leu)]

NM_000352.6(ABCC8):c.134C>T (p.Pro45Leu)

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.134C>T (p.Pro45Leu)

Other names:

ABCC8, 134C-T, PRO45LEU

HGVS:

NC_000011.10:g.17476643G>A
NG_008867.1:g.5260C>T
NM_000352.6:c.134C>TMANE SELECT
NM_001287174.3:c.134C>T
NM_001351295.2:c.134C>T
NM_001351296.2:c.134C>T
NM_001351297.2:c.134C>T
NP_000343.2:p.Pro45Leu
NP_001274103.1:p.Pro45Leu
NP_001338224.1:p.Pro45Leu
NP_001338225.1:p.Pro45Leu
NP_001338226.1:p.Pro45Leu
LRG_790t1:c.134C>T
LRG_790t2:c.134C>T
LRG_790:g.5260C>T
LRG_790p1:p.Pro45Leu
LRG_790p2:p.Pro45Leu
NC_000011.9:g.17498190G>A
NR_147094.2:n.203C>T
Q09428:p.Pro45Leu

Protein change:

P45L; PRO45LEU

Links:

UniProtKB: Q09428#VAR_072928; OMIM: 600509.0024; dbSNP: rs267606623

NCBI 1000 Genomes Browser:

rs267606623

Molecular consequence:

NM_000352.6:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.203C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440276	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17668386, 18025408, 25972930, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440276

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

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

Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.

Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks P, Shimomura K, Haberland H, Carson DJ, Shield JP, Hattersley AT, Ashcroft FM.

Am J Hum Genet. 2007 Aug;81(2):375-82. Epub 2007 Jun 29.

PubMed [citation]

PMID:: 17668386
PMCID:: PMC1950816

Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations.

Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT; Neonatal Diabetes International Collaborative Group..

Diabetes Care. 2008 Feb;31(2):204-9. Epub 2007 Nov 19.

PubMed [citation]

PMID:: 18025408
PMCID:: PMC7611807

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440276.1

#	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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 45 of the ABCC8 protein (p.Pro45Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with permanent neonatal diabetes mellitus (PMID: 17668386, 18025408, 25972930). ClinVar contains an entry for this variant (Variation ID: 9110). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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