NM_000545.8(HNF1A):c.1135C>A (p.Pro379Thr) AND Maturity onset diabetes mellitus in young

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 6, 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:: RCV004017808.2

Allele description [Variation Report for NM_000545.8(HNF1A):c.1135C>A (p.Pro379Thr)]

NM_000545.8(HNF1A):c.1135C>A (p.Pro379Thr)

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.1135C>A (p.Pro379Thr)

Other names:

NM_000545.8(HNF1A):c.1135C>A; p.Pro379Thr

HGVS:

NC_000012.12:g.120996568C>A
NG_011731.2:g.22823C>A
NM_000545.8:c.1135C>AMANE SELECT
NM_001306179.2:c.1135C>A
NP_000536.6:p.Pro379Thr
NP_001293108.2:p.Pro379Thr
LRG_522t1:c.1135C>A
LRG_522:g.22823C>A
NC_000012.11:g.121434371C>A
NC_000012.11:g.121434371C>A
NM_000545.5:c.1135C>A
NM_000545.6:c.1135C>A
NM_001306179.1:c.1135C>A

Protein change:

P379T

Links:

dbSNP: rs754729248

NCBI 1000 Genomes Browser:

rs754729248

Molecular consequence:

NM_000545.8:c.1135C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306179.2:c.1135C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity onset diabetes mellitus in young (MODY)
Synonyms:: Mason type diabetes
Identifiers:: MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848489	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Nov 6, 2020)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 30293189, 26479152, 28170077, 21683639, 28012402, 18003757, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848489

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Nov 6, 2020)

germline

clinical testing

PubMed (7)
[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

Screening of HNF1A and HNF4A mutation and clinical phenotype analysis in a large cohort of Chinese patients with maturity-onset diabetes of the young.

Wang X, Wang T, Yu M, Zhang H, Ping F, Zhang Q, Xu J, Feng K, Xiao X.

Acta Diabetol. 2019 Mar;56(3):281-288. doi: 10.1007/s00592-018-1232-x. Epub 2018 Oct 6.

PubMed [citation]

PMID:: 30293189

Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A-MODY cohort.

Bacon S, Kyithar MP, Rizvi SR, Donnelly E, McCarthy A, Burke M, Colclough K, Ellard S, Byrne MM.

Diabet Med. 2016 Jul;33(7):976-84. doi: 10.1111/dme.12992. Epub 2015 Nov 17.

PubMed [citation]

PMID:: 26479152

See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848489.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The p.Pro379Thr variant in HNF1A has been reported in at least 10 individuals with maturity-onset diabetes of the young (MODY) and segregated with disease in at least 6 affected relatives from 3 families (Wang 2019 PMID: 30293189, Kyithar 2011 21683639, Bacon 2016 26479152, Giuffrida 2017 28012402, Santana 2017 PMID: 28170077, Bellanné-Chantelot 2008 PMID: 18003757). It has been identified in 0.011% (4/35382) of Latino chromosomes and 0.002% (3/128426) European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The p.Pro379 codon is one of the most frequently mutated sites in the HNF1A gene (Ellard and Colclough 2013 PMID: 23348805). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant MODY. ACMG/AMP Criteria applied: PP1_Moderate, PM1, PP3, PS4_Moderate.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine