NM_000545.8(HNF1A):c.544C>T (p.Gln182Ter) AND Maturity onset diabetes mellitus in young

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 27, 2023
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:: RCV003388531.1

Allele description [Variation Report for NM_000545.8(HNF1A):c.544C>T (p.Gln182Ter)]

NM_000545.8(HNF1A):c.544C>T (p.Gln182Ter)

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.544C>T (p.Gln182Ter)

HGVS:

NC_000012.12:g.120993537C>T
NG_011731.2:g.19792C>T
NM_000545.8:c.544C>TMANE SELECT
NM_001306179.2:c.544C>T
NM_001406915.1:c.544C>T
NP_000536.5:p.Gln182Ter
NP_000536.6:p.Gln182Ter
NP_001293108.2:p.Gln182Ter
NP_001393844.1:p.Gln182Ter
LRG_522t1:c.544C>T
LRG_522:g.19792C>T
LRG_522p1:p.Gln182Ter
NC_000012.11:g.121431340C>T
NM_000545.5:c.544C>T
NM_000545.6:c.544C>T

Protein change:

Q182*

Molecular consequence:

NM_000545.8:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001306179.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406915.1:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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myc-associated zinc finger protein isoform 1 [Mus musculus]
myc-associated zinc finger protein isoform 1 [Mus musculus]
gi|114155153|ref|NP_034902.1|

Protein
Drug Overdose
Drug Overdose
Accidental or deliberate use of a medication or street drug in excess of normal dosage.<br/>Year introduced: 2013

MeSH
D062787 (1)
MeSH
Hemic and Lymphatic Diseases
Hemic and Lymphatic Diseases
Hematologic diseases and diseases of the lymphatic system collectively. Hemic diseases include disorders involving the formed elements (e.g., ERYTHROCYTE AGGREGATION, INTRAVAS...<br/>Year introduced: 1998

MeSH
RecName: Full=Myomegalin; AltName: Full=Cardiomyopathy-associated protein 2; Alt...
RecName: Full=Myomegalin; AltName: Full=Cardiomyopathy-associated protein 2; AltName: Full=Phosphodiesterase 4D-interacting protein
gi|1375381529|sp|Q5VU43.3|MYOME_HUM

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004100215	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23348805, 23771925 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004100215

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 27, 2023)

germline

clinical testing

PubMed (2)
[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 in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.

Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S.

Hum Mutat. 2013 May;34(5):669-85. doi: 10.1002/humu.22279. Epub 2013 Apr 2.

PubMed [citation]

PMID:: 23348805

Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth.

Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, Dolan LM, Greenbaum CJ, Imperatore G, Lawrence JM, Marcovina SM, Mayer-Davis E, Rodriguez BL, Steck AK, Williams DE, Hattersley AT; SEARCH for Diabetes in Youth Study Group..

J Clin Endocrinol Metab. 2013 Oct;98(10):4055-62. doi: 10.1210/jc.2013-1279. Epub 2013 Jun 14.

PubMed [citation]

PMID:: 23771925
PMCID:: PMC3790621

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004100215.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: HNF1A c.544C>T (p.Gln182X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251276 control chromosomes (gnomAD). c.544C>T has been reported in the literature in individuals affected with Maturity Onset Diabetes Of The Young (e.g. Colclough_2013, Pihoker_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23348805, 23771925). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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 4, 2023

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