NM_000545.8(HNF1A):c.1424C>T (p.Pro475Leu) AND Maturity onset diabetes mellitus in young

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 20, 2021
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:: RCV002390124.2

Allele description [Variation Report for NM_000545.8(HNF1A):c.1424C>T (p.Pro475Leu)]

NM_000545.8(HNF1A):c.1424C>T (p.Pro475Leu)

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.1424C>T (p.Pro475Leu)

Other names:

NM_000545.8(HNF1A):c.1424C>T

HGVS:

NC_000012.12:g.120997588C>T
NG_011731.2:g.23843C>T
NM_000545.6:c.1424C>T
NM_000545.8:c.1424C>TMANE SELECT
NM_001306179.2:c.1424C>T
NP_000536.6:p.Pro475Leu
NP_001293108.2:p.Pro475Leu
LRG_522t1:c.1424C>T
LRG_522:g.23843C>T
NC_000012.11:g.121435391C>T
NM_000545.5:c.1424C>T
NM_000545.6(HNF1A):c.1424C>T

Protein change:

P475L

Links:

dbSNP: rs193922580

NCBI 1000 Genomes Browser:

rs193922580

Molecular consequence:

NM_000545.8:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001306179.2:c.1424C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002702712	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 20, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18811724, 31363388, 32684311 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002702712

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 20, 2021)

germline

clinical testing

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	clinical testing

Citations

PubMed

Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

Plengvidhya N, Boonyasrisawat W, Chongjaroen N, Jungtrakoon P, Sriussadaporn S, Vannaseang S, Banchuin N, Yenchitsomanus PT.

Clin Endocrinol (Oxf). 2009 Jun;70(6):847-53. doi: 10.1111/j.1365-2265.2008.03397.x. Epub 2008 Sep 22.

PubMed [citation]

PMID:: 18811724

HNF1A mutation in a Thai patient with maturity-onset diabetes of the young: A case report.

Plengvidhya N, Tangjittipokin W, Teerawattanapong N, Narkdontri T, Yenchitsomanus PT.

World J Diabetes. 2019 Jul 15;10(7):414-420. doi: 10.4239/wjd.v10.i7.414.

PubMed [citation]

PMID:: 31363388
PMCID:: PMC6656704

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002702712.2

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

Description

The p.P475L variant (also known as c.1424C>T), located in coding exon 7 of the HNF1A gene, results from a C to T substitution at nucleotide position 1424. The proline at codon 475 is replaced by leucine, an amino acid with similar properties. This alteration has been reported in a Thai subject with type 2 diabetes (Plengvidhya N et al. Clin Endocrinol (Oxf), 2009 Jun;70:847-53). This variant has been noted to have reduced transactivation activity and affected cell cycle and growth (Sujjitjoon J et al. Biochem Biophys Res Commun, 2020 Aug;529:826-833). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 26, 2024

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