NM_000545.8(HNF1A):c.1380_1406del (p.Gln460_Leu468del) AND Maturity onset diabetes mellitus in young

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 6, 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:: RCV002319699.5

Allele description [Variation Report for NM_000545.8(HNF1A):c.1380_1406del (p.Gln460_Leu468del)]

NM_000545.8(HNF1A):c.1380_1406del (p.Gln460_Leu468del)

Gene:

HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000545.8(HNF1A):c.1380_1406del (p.Gln460_Leu468del)

HGVS:

NC_000012.12:g.120997544_120997570del
NG_011731.2:g.23799_23825del
NM_000545.6:c.1380_1406del
NM_000545.8:c.1380_1406delMANE SELECT
NM_001306179.2:c.1380_1406del
NP_000536.6:p.Gln460_Leu468del
NP_001293108.2:p.Gln460_Leu468del
LRG_522t1:c.1380_1406del
LRG_522:g.23799_23825del
NC_000012.11:g.121435342_121435368del
NC_000012.11:g.121435347_121435373del
NM_000545.5:c.1380_1406del
NM_000545.5:c.1380_1406del27

Links:

dbSNP: rs544842497

NCBI 1000 Genomes Browser:

rs544842497

Molecular consequence:

NM_000545.8:c.1380_1406del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001306179.2:c.1380_1406del - inframe_deletion - [Sequence Ontology: SO:0001822]

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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PGAP3 [Puma concolor]
Gene ID:112854128

Gene
CANX [Puma concolor]
CANX [Puma concolor]
Gene ID:112861376

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002604919	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)	Likely benign	unknown	research	PubMed (4) [See all records that cite these PMIDs] 31517624, 32395877, 35328643, 35673428 Citation Link,
SCV002696454	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 6, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002604919

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)

Likely benign

unknown

research

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV002696454

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 6, 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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Novel insights into genetics and clinics of the HNF1A-MODY.

Valkovicova T, Skopkova M, Stanik J, Gasperikova D.

Endocr Regul. 2019 Apr 1;53(2):110-134. doi: 10.2478/enr-2019-0013. Review.

PubMed [citation]

PMID:: 31517624

Altered cortisol metabolism in individuals with HNF1A-MODY.

Juszczak A, Gilligan LC, Hughes BA, Hassan-Smith ZK, McCarthy MI, Arlt W, Tomlinson JW, Owen KR.

Clin Endocrinol (Oxf). 2020 Sep;93(3):269-279. doi: 10.1111/cen.14218. Epub 2020 Jun 5.

PubMed [citation]

PMID:: 32395877

See all PubMed Citations (4)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002604919.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	research	PubMed (4)

Description

Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs544842497 with MODY3.

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

From Ambry Genetics, SCV002696454.2

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

Description

The c.1380_1406del27 variant (also known as p.Q460_L468del) is located in coding exon 7 of the HNF1A gene. This variant results from an in-frame deletion of 27 nucleotides at positions 1380 to 1046. This results in the deletion of 9 residues between codons 460 and 468. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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