NM_000209.4(PDX1):c.670G>A (p.Glu224Lys) AND Type 2 diabetes mellitus

Germline classification:: Uncertain significance (1 submission)
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:: RCV001258264.4

Allele description [Variation Report for NM_000209.4(PDX1):c.670G>A (p.Glu224Lys)]

NM_000209.4(PDX1):c.670G>A (p.Glu224Lys)

Gene:

PDX1:pancreatic and duodenal homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.2

Genomic location:

Preferred name:

NM_000209.4(PDX1):c.670G>A (p.Glu224Lys)

HGVS:

NC_000013.11:g.27924519G>A
NG_008183.1:g.9489G>A
NM_000209.4:c.670G>AMANE SELECT
NP_000200.1:p.Glu224Lys
NC_000013.10:g.28498656G>A
NM_000209.3:c.670G>A

Protein change:

E224K; GLU224LYS

Links:

OMIM: 600733.0007; dbSNP: rs137852787

NCBI 1000 Genomes Browser:

rs137852787

Molecular consequence:

NM_000209.4:c.670G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Type 2 diabetes mellitus
Synonyms:: DIABETES MELLITUS, TYPE 2, PROTECTION AGAINST; Type II diabetes mellitus; Diabetes mellitus, noninsulin-dependent, late onset
Identifiers:: MONDO: MONDO:0005148; MeSH: D003924; MedGen: C0011860; OMIM: 125853; Human Phenotype Ontology: HP:0005978

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001435184	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	research	PubMed (2) [See all records that cite these PMIDs] 14764823, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001435184

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

research

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family.

Cockburn BN, Bermano G, Boodram LL, Teelucksingh S, Tsuchiya T, Mahabir D, Allan AB, Stein R, Docherty K, Bell GI.

J Clin Endocrinol Metab. 2004 Feb;89(2):971-8.

PubMed [citation]

PMID:: 14764823

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001435184.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

The heterozygous p.Glu224Lys variant in PDX1 has been identified in at least 2 individuals with type 2 diabetes mellitus (PMID: 14764823), but has also been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Glu224Lys variant may slightly impact protein function (PMID: 14764823). However, these types of assays may not accurately represent biological function. In summary, the clinical significance of this variant is uncertain.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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