NM_000458.4(HNF1B):c.73G>T (p.Val25Leu) AND Maturity onset diabetes mellitus in young

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 16, 2017
Review status:: criteria provided, conflicting classifications

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:: RCV002250467.12

Allele description [Variation Report for NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)]

NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)

Gene:

HNF1B:HNF1 homeobox B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)

HGVS:

NC_000017.11:g.37744812C>A
NG_013019.2:g.5295G>T
NM_000458.4:c.73G>TMANE SELECT
NM_001165923.4:c.73G>T
NM_001304286.2:c.73G>T
NP_000449.1:p.Val25Leu
NP_001159395.1:p.Val25Leu
NP_001291215.1:p.Val25Leu
NC_000017.10:g.36104803C>A
NM_000458.2:c.73G>T
NM_000458.3:c.73G>T

Protein change:

V25L

Links:

dbSNP: rs139107479

NCBI 1000 Genomes Browser:

rs139107479

Molecular consequence:

NM_000458.4:c.73G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165923.4:c.73G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304286.2:c.73G>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
SCV002520721	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Uncertain significance	somatic	research	PubMed (2) [See all records that cite these PMIDs] 33259036, 31825128 Citation Link,
SCV002673082	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Nov 16, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520721

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

criteria provided, single submitter

(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)

Uncertain significance

somatic

research

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

Citation Link,

SCV002673082

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Benign
(Nov 16, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prenatal diagnosis of HNF1b mutation allows recognition of neonatal dysglycemia.

Iafusco F, Meola S, Pecoraro C, Mazzaccara C, Iafusco D, Tinto N.

Acta Diabetol. 2021 Mar;58(3):393-395. doi: 10.1007/s00592-020-01641-2. Epub 2020 Dec 1. No abstract available.

PubMed [citation]

PMID:: 33259036
PMCID:: PMC7906928

A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes.

Sztromwasser P, Michalak A, Małachowska B, Młudzik P, Antosik K, Hogendorf A, Zmysłowska A, Borowiec M, Młynarski W, Fendler W.

Pediatr Diabetes. 2020 May;21(3):422-430. doi: 10.1111/pedi.12959. Epub 2020 Jan 29.

PubMed [citation]

PMID:: 31825128
PMCID:: PMC7217165

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002520721.1

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

Description

Mutations in HNF1B gene are generally associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia. However, no sufficient evidence is found for the role of this particular variant (rs139107479) of HNF1B in Diabetes Mellitus or MODY yet.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	somatic	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002673082.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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: Jan 13, 2025

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