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NM_175914.5(HNF4A):c.335G>A (p.Arg112Gln) AND Maturity-onset diabetes of the young type 1

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jun 23, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV002285340.7

Allele description [Variation Report for NM_175914.5(HNF4A):c.335G>A (p.Arg112Gln)]

NM_175914.5(HNF4A):c.335G>A (p.Arg112Gln)

Gene:
HNF4A:hepatocyte nuclear factor 4 alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.12
Genomic location:
Preferred name:
NM_175914.5(HNF4A):c.335G>A (p.Arg112Gln)
Other names:
NM_175914.5(HNF4A):c.335G>A; p.Arg112Gln
HGVS:
  • NC_000020.11:g.44413709G>A
  • NG_009818.1:g.62909G>A
  • NM_000457.6:c.401G>A
  • NM_001030003.3:c.335G>A
  • NM_001030004.3:c.335G>A
  • NM_001258355.2:c.380G>A
  • NM_001287182.2:c.326G>A
  • NM_001287183.2:c.326G>A
  • NM_001287184.2:c.326G>A
  • NM_175914.5:c.335G>AMANE SELECT
  • NM_178849.3:c.401G>A
  • NM_178850.3:c.401G>A
  • NP_000448.3:p.Arg134Gln
  • NP_000448.3:p.Arg134Gln
  • NP_001025174.1:p.Arg112Gln
  • NP_001025175.1:p.Arg112Gln
  • NP_001245284.1:p.Arg127Gln
  • NP_001274111.1:p.Arg109Gln
  • NP_001274112.1:p.Arg109Gln
  • NP_001274113.1:p.Arg109Gln
  • NP_787110.2:p.Arg112Gln
  • NP_849180.1:p.Arg134Gln
  • NP_849181.1:p.Arg134Gln
  • LRG_483t1:c.335G>A
  • LRG_483t2:c.401G>A
  • LRG_483:g.62909G>A
  • LRG_483p2:p.Arg134Gln
  • NC_000020.10:g.43042349G>A
  • NM_000457.4:c.401G>A
  • NM_175914.3:c.335G>A
  • NM_175914.4:c.335G>A
Protein change:
R109Q
Links:
dbSNP: rs1085307913
NCBI 1000 Genomes Browser:
rs1085307913
Molecular consequence:
  • NM_000457.6:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030003.3:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030004.3:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258355.2:c.380G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287182.2:c.326G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287183.2:c.326G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287184.2:c.326G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_175914.5:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178849.3:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178850.3:c.401G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Maturity-onset diabetes of the young type 1
Synonyms:
MILD JUVENILE DIABETES MELLITUS; MODY type 1; Diabetes mellitus MODY type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007452; MedGen: C1852093; Orphanet: 552; OMIM: 125850

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002562172Geisinger Clinic, Geisinger Health System
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 2, 2022) 		germlineresearch

PubMed (2)
[See all records that cite these PMIDs]

SCV004045963Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
criteria provided, single submitter

(Classification criteria August 2017)		Pathogenic
(Jun 23, 2023) 		de novoclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyes1not providednot providednot providednot providedclinical testing
not providedgermlineyes1not providednot providednot providednot providedresearch

Citations

PubMed

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

Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.

Mirshahi UL, Colclough K, Wright CF, Wood AR, Beaumont RN, Tyrrell J, Laver TW, Stahl R, Golden A, Goehringer JM; Geisinger-Regeneron DiscovEHR Collaboration., Frayling TF, Hattersley AT, Carey DJ, Weedon MN, Patel KA.

Am J Hum Genet. 2022 Nov 3;109(11):2018-2028. doi: 10.1016/j.ajhg.2022.09.014. Epub 2022 Oct 17.

PubMed [citation]
PMID:
36257325
PMCID:
PMC9674944

Details of each submission

From Geisinger Clinic, Geisinger Health System, SCV002562172.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (2)

Description

PS4, PP1_Strong, PP4_Moderate, PM2, PP3, PM1, PM5_Supporting

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV004045963.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024