U.S. flag

An official website of the United States government

NM_000545.8(HNF1A):c.608G>A (p.Arg203His) AND HNF1A-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 29, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004752747.1

Allele description [Variation Report for NM_000545.8(HNF1A):c.608G>A (p.Arg203His)]

NM_000545.8(HNF1A):c.608G>A (p.Arg203His)

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.608G>A (p.Arg203His)
Other names:
NM_000545.6(HNF1A):c.608G>A; p.Arg203His
HGVS:
  • NC_000012.12:g.120993601G>A
  • NG_011731.2:g.19856G>A
  • NM_000545.8:c.608G>AMANE SELECT
  • NM_001306179.2:c.608G>A
  • NP_000536.6:p.Arg203His
  • NP_001293108.2:p.Arg203His
  • LRG_522t1:c.608G>A
  • LRG_522:g.19856G>A
  • NC_000012.11:g.121431404G>A
  • NM_000545.5:c.608G>A
  • NM_000545.6:c.608G>A
Protein change:
R203H
Links:
dbSNP: rs587780357
NCBI 1000 Genomes Browser:
rs587780357
Molecular consequence:
  • NM_000545.8:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306179.2:c.608G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
HNF1A-related disorder
Synonyms:
HNF1A-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005362210PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Feb 29, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005362210.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The HNF1A c.608G>A variant is predicted to result in the amino acid substitution p.Arg203His. This variant has been reported in several individuals with maturity-onset diabetes of the young (MODY) (see examples: Ng et al. 1999. PubMed ID: 10588527; Wang et al. 2018. PubMed ID: 30293189; Ma et al. 2020. PubMed ID: 32238361; Thanabalasingham et al. 2012. PubMed ID: 23274891; Wang DW et al 2022. PubMed ID: 35921062). In vitro functional studies demonstrate that expression of this variant results in protein mislocalization and reduced DNA binding ability compared to wild-type (Bjørkhaug L et al 2005. PubMed ID: 16274290; Figure S5, Althari et al. 2020. PubMed ID: 32910913). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. This variant has been interpreted as pathogenic by the ClinGen monogenic diabetes variant curation expert panel (VCEP, https://www.ncbi.nlm.nih.gov/clinvar/variation/129235/). Additionally, different missense changes impacting the same amino acid (p.Arg203Ser, p.Arg203Gly, p.Arg203Cys) have been reported in individuals with MODY (Colclough et al. 2013. PubMed ID: 23348805; Lopez et al. 2011. PubMed ID: 21168233). Taken together, the c.608G>A (p.Arg205His) variant is interpreted as pathogenic.

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

Last Updated: Oct 13, 2024