Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_001306179.2:c.14T>G

CA386952150

1342945 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 688785d0-467c-4dc3-b232-ecfeb9dfc07b

Approved on: 2022-02-22

Published on: 2022-07-11

HGVS expressions

NM_001306179.2:c.14T>G

NC_000012.12:g.120978782T>G

CM000674.2:g.120978782T>G

NC_000012.11:g.121416585T>G

CM000674.1:g.121416585T>G

NC_000012.10:g.119900968T>G

NG_011731.2:g.5037T>G

ENST00000257555.11:c.14T>G

ENST00000257555.10:c.14T>G

ENST00000400024.6:c.14T>G

ENST00000402929.5:n.149T>G

ENST00000535955.5:n.42+90T>G

ENST00000538626.2:n.132T>G

ENST00000538646.5:c.14T>G

ENST00000540108.1:c.14T>G

ENST00000541395.5:c.14T>G

ENST00000541924.5:c.14T>G

ENST00000543427.5:c.14T>G

ENST00000544413.2:c.14T>G

ENST00000544574.5:c.14T>G

ENST00000560968.5:n.157T>G

ENST00000615446.4:c.-258+71T>G

ENST00000617366.4:c.14T>G

NM_000545.5:c.14T>G

NM_000545.6:c.14T>G

NM_001306179.1:c.14T>G

NM_000545.8:c.14T>G

NM_000545.8(HNF1A):c.14T>G (p.Leu5Arg)

Uncertain Significance

PM1_Supporting PM2_Supporting PP3

PP4

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.14T>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of leucine to arginine at codon 5 (p.(Leu5Arg) of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting).  Additionally, this variant is located within the DNA dimerization domain of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting).  This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (PMID: 23348805, internal lab contributor). Lastly, this variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.934, which is greater than the MDEP threshold of 0.70 (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM2_Supporting, PM1_Supporting, PP3.

PM1_Supporting

This variant is located within the DNA dimerization domain of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting). 

PP3

This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.934, which is greater than the MDEP threshold of 0.70 (PP3).

PP4

This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (PMID: 23348805, internal lab contributor).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.