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NM_000352.6(ABCC8):c.403C>G (p.Leu135Val) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 11, 2024
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:
RCV002527449.5

Allele description [Variation Report for NM_000352.6(ABCC8):c.403C>G (p.Leu135Val)]

NM_000352.6(ABCC8):c.403C>G (p.Leu135Val)

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.403C>G (p.Leu135Val)
HGVS:
  • NC_000011.10:g.17470110G>C
  • NG_008867.1:g.11793C>G
  • NM_000352.6:c.403C>GMANE SELECT
  • NM_001287174.3:c.403C>G
  • NM_001351295.2:c.403C>G
  • NM_001351296.2:c.403C>G
  • NM_001351297.2:c.403C>G
  • NP_000343.2:p.Leu135Val
  • NP_001274103.1:p.Leu135Val
  • NP_001338224.1:p.Leu135Val
  • NP_001338225.1:p.Leu135Val
  • NP_001338226.1:p.Leu135Val
  • LRG_790t1:c.403C>G
  • LRG_790t2:c.403C>G
  • LRG_790:g.11793C>G
  • LRG_790p1:p.Leu135Val
  • LRG_790p2:p.Leu135Val
  • NC_000011.9:g.17491657G>C
  • NM_000352.3:c.403C>G
  • NM_000352.5:c.403C>G
  • NR_147094.2:n.472C>G
  • p.LEU135VAL
Protein change:
L135V
Links:
dbSNP: rs368450282
NCBI 1000 Genomes Browser:
rs368450282
Molecular consequence:
  • NM_000352.6:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287174.3:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351295.2:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351296.2:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351297.2:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147094.2:n.472C>G - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003440253Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 11, 2024) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension.

Bohnen MS, Ma L, Zhu N, Qi H, McClenaghan C, Gonzaga-Jauregui C, Dewey FE, Overton JD, Reid JG, Shuldiner AR, Baras A, Sampson KJ, Bleda M, Hadinnapola C, Haimel M, Bogaard HJ, Church C, Coghlan G, Corris PA, Eyries M, Gibbs JSR, Girerd B, et al.

Circ Genom Precis Med. 2018 Oct;11(10):e002087. doi: 10.1161/CIRCGEN.118.002087.

PubMed [citation]
PMID:
30354297
PMCID:
PMC6206877
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440253.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 135 of the ABCC8 protein (p.Leu135Val). This variant is present in population databases (rs368450282, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive diffuse congenital hyperinsulinism (PMID: 20685672). ClinVar contains an entry for this variant (Variation ID: 446772). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCC8 protein function. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 30354297). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2025