NM_000352.6(ABCC8):c.4432G>A (p.Gly1478Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000710389.3

Allele description [Variation Report for NM_000352.6(ABCC8):c.4432G>A (p.Gly1478Arg)]

NM_000352.6(ABCC8):c.4432G>A (p.Gly1478Arg)

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.4432G>A (p.Gly1478Arg)
HGVS:
  • NC_000011.10:g.17394379C>T
  • NG_008867.1:g.87524G>A
  • NM_000352.6:c.4432G>AMANE SELECT
  • NM_001287174.3:c.4435G>A
  • NM_001351295.2:c.4498G>A
  • NM_001351296.2:c.4432G>A
  • NM_001351297.2:c.4429G>A
  • NP_000343.2:p.Gly1478Arg
  • NP_001274103.1:p.Gly1479Arg
  • NP_001338224.1:p.Gly1500Arg
  • NP_001338225.1:p.Gly1478Arg
  • NP_001338226.1:p.Gly1477Arg
  • LRG_790t1:c.4432G>A
  • LRG_790t2:c.4435G>A
  • LRG_790:g.87524G>A
  • LRG_790p1:p.Gly1478Arg
  • LRG_790p2:p.Gly1479Arg
  • NC_000011.9:g.17415926C>T
  • NM_000352.3:c.4432G>A
  • NM_000352.4:c.4432G>A
  • NR_147094.2:n.4727G>A
Protein change:
G1477R
Links:
dbSNP: rs72559715
NCBI 1000 Genomes Browser:
rs72559715
Molecular consequence:
  • NM_000352.6:c.4432G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287174.3:c.4435G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351295.2:c.4498G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351296.2:c.4432G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351297.2:c.4429G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147094.2:n.4727G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000840599Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Jun 25, 2018)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001582811Invitaecriteria provided, single submitter
Pathogenic
(Oct 19, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains.

Kelly L, Fukushima H, Karchin R, Gow JM, Chinn LW, Pieper U, Segal MR, Kroetz DL, Sali A.

Protein Sci. 2010 Nov;19(11):2110-21. doi: 10.1002/pro.491.

PubMed [citation]
PMID:
20799350
PMCID:
PMC3005782

Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations.

Pinney SE, MacMullen C, Becker S, Lin YW, Hanna C, Thornton P, Ganguly A, Shyng SL, Stanley CA.

J Clin Invest. 2008 Aug;118(8):2877-86. doi: 10.1172/JCI35414.

PubMed [citation]
PMID:
18596924
PMCID:
PMC2441858
See all PubMed Citations (11)

Details of each submission

From Athena Diagnostics Inc, SCV000840599.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001582811.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine with arginine at codon 1478 of the ABCC8 protein (p.Gly1478Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant congenital hyperinsulinism and autosomal dominant ABCC8-related early onset diabetes (PMID: 19475716, 30977832, 30098243). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 434045). 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. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 20, 2021

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