NM_000545.8(HNF1A):c.871C>A (p.Pro291Thr) AND Maturity-onset diabetes of the young type 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2020
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:: RCV001249071.6

Allele description [Variation Report for NM_000545.8(HNF1A):c.871C>A (p.Pro291Thr)]

NM_000545.8(HNF1A):c.871C>A (p.Pro291Thr)

Gene:

HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000545.8(HNF1A):c.871C>A (p.Pro291Thr)

Other names:

NM_000545.8(HNF1A):c.871C>A; p.Pro291Thr

HGVS:

NC_000012.12:g.120994321C>A
NG_011731.2:g.20576C>A
NM_000545.8:c.871C>AMANE SELECT
NM_001306179.2:c.871C>A
NP_000536.6:p.Pro291Thr
NP_001293108.2:p.Pro291Thr
LRG_522:g.20576C>A
NC_000012.11:g.121432124C>A
NC_000012.11:g.121432124C>A
NM_001306179.1:c.871C>A

Protein change:

P291T

Links:

dbSNP: rs151256267

NCBI 1000 Genomes Browser:

rs151256267

Molecular consequence:

NM_000545.8:c.871C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306179.2:c.871C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity-onset diabetes of the young type 3
Synonyms:: Diabetes mellitus MODY type 3; MODY hepatocyte nuclear factor-1-alpha related; MODY type 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010894; MedGen: C1838100; Orphanet: 552; OMIM: 600496

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001423019	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 18003757, 30455330, 25741868 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001423019

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

germline

curation

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

Citation Link

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	curation

Citations

PubMed

The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3.

Bellanné-Chantelot C, Carette C, Riveline JP, Valéro R, Gautier JF, Larger E, Reznik Y, Ducluzeau PH, Sola A, Hartemann-Heurtier A, Lecomte P, Chaillous L, Laloi-Michelin M, Wilhem JM, Cuny P, Duron F, Guerci B, Jeandidier N, Mosnier-Pudar H, Assayag M, Dubois-Laforgue D, Velho G, et al.

Diabetes. 2008 Feb;57(2):503-8. Epub 2007 Nov 14.

PubMed [citation]

PMID:: 18003757

Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult-Onset Nonautoimmune Diabetes.

Juszczak A, Pavić T, Vučković F, Bennett AJ, Shah N, Pape Medvidović E, Groves CJ, Šekerija M, Chandler K, Burrows C, Rojnić Putarek N, Vučić Lovrenčić M, Ćuća Knežević J, James TJ, Gloyn AL, Lauc G, McCarthy MI, Owen KR, Gornik O.

Diabetes Care. 2019 Jan;42(1):17-26. doi: 10.2337/dc18-0422. Epub 2018 Nov 19.

PubMed [citation]

PMID:: 30455330

See all PubMed Citations (3)

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001423019.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

Description

The p.Pro291Thr variant in HNF1A has been reported in at least 2 European individuals with maturity-onset diabetes of the young (PMID: 18003757, 30455330), and has been identified in 0.006% (2/33380) of Latino chromosomes and 0.0009% (1/108298) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs151256267). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. In vitro functional studies provide some evidence that the p.Pro291Thr variant may slightly impact protein function (PMID: 30455330). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PS4_Supporting, PS3_Supporting (Richards 2015).

#	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: Nov 3, 2024

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