NM_000458.4(HNF1B):c.544C>T (p.Gln182Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 29, 2023
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:: RCV000713802.10

Allele description

NM_000458.4(HNF1B):c.544C>T (p.Gln182Ter)

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.544C>T (p.Gln182Ter)

HGVS:

NC_000017.11:g.37739440G>A
NG_013019.2:g.10667C>T
NM_000458.4:c.544C>TMANE SELECT
NM_001165923.4:c.544C>T
NM_001304286.2:c.544C>T
NP_000449.1:p.Gln182Ter
NP_001159395.1:p.Gln182Ter
NP_001291215.1:p.Gln182Ter
NC_000017.10:g.36099431G>A
NM_000458.2:c.544C>T
NM_000458.3:c.544C>T

Protein change:

Q182*

Links:

Molecular consequence:

NM_000458.4:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001165923.4:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001304286.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000844438	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Aug 13, 2018)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22706971, 25500806, 21163139, 15068978, 18528323, 26467025
SCV000890277	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 25, 2018)	germline	clinical testing	Citation Link,
SCV002148920	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 29, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 22706971, 25500806, 9398836, 12148114, 15068978, 20378641, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000844438

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Aug 13, 2018)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV000890277

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 25, 2018)

germline

clinical testing

Citation Link,

SCV002148920

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 29, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5.

Chen YZ, Gao Q, Zhao XZ, Chen YZ, Bennett CL, Xiong XS, Mei CL, Shi YQ, Chen XM.

Chin Med J (Engl). 2010 Nov;123(22):3326-33. Review.

PubMed [citation]

PMID:: 21163139

A genetic syndrome of chronic renal failure with multiple renal cysts and early onset diabetes.

Thomas CP, Erlandson JC, Edghill EL, Hattersley AT, Stolpen AH.

Kidney Int. 2008 Oct;74(8):1094-9. doi: 10.1038/ki.2008.227. Epub 2008 Jun 4. No abstract available.

PubMed [citation]

PMID:: 18528323

See all PubMed Citations (10)

Details of each submission

From Athena Diagnostics, SCV000844438.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

#	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

From GeneDx, SCV000890277.1

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

Description

The Q182X variant in the HNF1B gene has been reported previously in individuals with features of HNF1B-related disorders (Bellanne-Chantelot et al., 2004; Roelandt et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q182X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Q182X as a pathogenic variant.

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

From Invitae, SCV002148920.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 586801). This premature translational stop signal has been observed in individual(s) with HNF1B-related conditions (PMID: 15068978, 22706971, 25500806). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln182*) in the HNF1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HNF1B are known to be pathogenic (PMID: 9398836, 12148114, 15068978, 20378641).

#	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 16, 2024

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