NM_000545.8(HNF1A):c.1310-1G>A AND Maturity onset diabetes mellitus in young

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 24, 2024
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:: RCV002319670.2

Allele description [Variation Report for NM_000545.8(HNF1A):c.1310-1G>A]

NM_000545.8(HNF1A):c.1310-1G>A

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.1310-1G>A

HGVS:

NC_000012.12:g.120997473G>A
NG_011731.2:g.23728G>A
NM_000545.8:c.1310-1G>AMANE SELECT
NM_001306179.2:c.1310-1G>A
NM_001406915.1:c.1309+731G>A
LRG_522:g.23728G>A
NC_000012.11:g.121435276G>A
NM_000545.6:c.1310-1G>A

Links:

dbSNP: rs1877168655

NCBI 1000 Genomes Browser:

rs1877168655

Molecular consequence:

NM_001406915.1:c.1309+731G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000545.8:c.1310-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001306179.2:c.1310-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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cytochrome oxidase subunit I, partial (mitochondrion) [Chrysomya chloropyga]
cytochrome oxidase subunit I, partial (mitochondrion) [Chrysomya chloropyga]
gi|1489635944|gb|AYI63784.1|

Protein
cytochrome c oxidase subunit I, partial (mitochondrion) [Chrysomya chloropyga]
cytochrome c oxidase subunit I, partial (mitochondrion) [Chrysomya chloropyga]
gi|2060267855|gb|QXF10225.1|

Protein
N,N'-diacetylbacillosaminyl-diphospho-undecaprenol alpha-1,3-N-acetylgalactosami...
N,N'-diacetylbacillosaminyl-diphospho-undecaprenol alpha-1,3-N-acetylgalactosaminyltransferase [Bacteroides fragilis]
gi|2759685420|gnl|PRJNA982086|QR311 2|gb|XCP07176.1|

Protein
Mus musculus voltage-dependent anion channel 3 (Vdac3), transcript variant 2, mR...
Mus musculus voltage-dependent anion channel 3 (Vdac3), transcript variant 2, mRNA
gi|312222782|ref|NM_011696.2|

Nucleotide
JGI_XZG38570.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7553637 3'...
JGI_XZG38570.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7553637 3', mRNA sequence
gi|57404116|gnl|dbEST|27113931|gb|C 70.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002604918	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 pathogenic	unknown	research	PubMed (4) [See all records that cite these PMIDs] 31517624, 32395877, 35328643, 35673428 Citation Link,
SCV005076612	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 24, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002604918

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 pathogenic

unknown

research

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

Citation Link,

SCV005076612

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 24, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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 (5)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002604918.1

#	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 rs1877168655 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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005076612.1

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

Description

Variant summary: HNF1A c.1310-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246036 control chromosomes. c.1310-1G>A has been reported in the literature in at least one individual affected with type 1 diabetes (Marchand_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 33538814). ClinVar contains an entry for this variant (Variation ID: 916727). Based on the evidence outlined above, the variant was classified as likely 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: Jul 23, 2024

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