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NM_000458.4(HNF1B):c.1338A>G (p.Gln446=) AND Maturity onset diabetes mellitus in young

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Nov 19, 2022
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_000458.4(HNF1B):c.1338A>G (p.Gln446=)]

NM_000458.4(HNF1B):c.1338A>G (p.Gln446=)

HNF1B:HNF1 homeobox B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000458.4(HNF1B):c.1338A>G (p.Gln446=)
  • NC_000017.11:g.37704918T>C
  • NG_013019.2:g.45189A>G
  • NM_000458.2:c.1338A>G
  • NM_000458.4:c.1338A>GMANE SELECT
  • NM_001165923.4:c.1260A>G
  • NM_001304286.2:c.1260A>G
  • NP_000449.1:p.Gln446=
  • NP_001159395.1:p.Gln420=
  • NP_001291215.1:p.Gln420=
  • NC_000017.10:g.36064925T>C
dbSNP: rs776536485
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000458.4:c.1338A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001165923.4:c.1260A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001304286.2:c.1260A>G - synonymous variant - [Sequence Ontology: SO:0001819]


Maturity onset diabetes mellitus in young (MODY)
Mason type diabetes
MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV002605567Clinical 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 significanceunknownresearch

PubMed (8)
[See all records that cite these PMIDs]

Citation Link,

SCV003863687Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely benign
(Nov 19, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

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



The HNF1B score is a simple tool to select patients for HNF1B gene analysis.

Faguer S, Chassaing N, Bandin F, Prouheze C, Garnier A, Casemayou A, Huart A, Schanstra JP, Calvas P, Decramer S, Chauveau D.

Kidney Int. 2014 Nov;86(5):1007-15. doi: 10.1038/ki.2014.202. Epub 2014 Jun 4. Review.

PubMed [citation]

HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum.

Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C.

Nat Rev Nephrol. 2015 Feb;11(2):102-12. doi: 10.1038/nrneph.2014.232. Epub 2014 Dec 23. Review.

PubMed [citation]
See all PubMed Citations (8)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002605567.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providedresearch PubMed (8)


HNF1B gene mutations are 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 to ascertain the role of this particular variant rs776536485, yet.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV003863687.2

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


This alteration is classified as likely 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.

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

Last Updated: May 1, 2024