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]

Variant: NM_001306179.2:c.225C>G

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA386953857

1676701 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2e8b0e51-77c1-478f-b123-9a1f1a8dbb65

Approved on: 2025-11-26

Published on: 2025-11-26

HGVS expressions

NM_001306179.2:c.225C>G

NC_000012.12:g.120978993C>G

CM000674.2:g.120978993C>G

NC_000012.11:g.121416796C>G

CM000674.1:g.121416796C>G

NC_000012.10:g.119901179C>G

NG_011731.2:g.5248C>G

ENST00000560968.6:c.225C>G

ENST00000257555.11:c.225C>G

ENST00000257555.10:c.225C>G

ENST00000400024.6:c.225C>G

ENST00000402929.5:n.360C>G

ENST00000535955.5:n.42+301C>G

ENST00000538626.2:n.190+153C>G

ENST00000538646.5:c.225C>G

ENST00000540108.1:c.225C>G

ENST00000541395.5:c.225C>G

ENST00000541924.5:c.225C>G

ENST00000543427.5:c.225C>G

ENST00000544413.2:c.225C>G

ENST00000544574.5:c.72+153C>G

ENST00000560968.5:c.368C>G

ENST00000615446.4:c.-258+282C>G

ENST00000617366.4:c.225C>G

NM_000545.5:c.225C>G

NM_000545.6:c.225C>G

NM_001306179.1:c.225C>G

NM_000545.8:c.225C>G

Uncertain Significance

PM2_Supporting

PS1 PP3 PM1 BP4

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 for HNF1A Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.225C>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of asparagine to glutamate at codon 75 (p.(Asp75Glu)) of NM_000545.8. This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to the presence of one copy in the African/African American subpopulation and 0 copies in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting. This variant has a REVEL score of 0.564, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function. The nucleotide change c.225C>G, which causes the same amino acid change, was classified as a VUS by by the ClinGen MDEP; therefore, PS1 will not be applied. In summary, c.225C>G 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 3.1.0 approved 10/10/2025): PM2_Supporting.

PM2_Supporting

This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to the presence of one copy in the African/African American subpopulation and 0 copies in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting.

PS1

The nucleotide change c.225C>A, which causes the same amino acid change, was classified as a VUS by by the ClinGen MDEP.

PP3

This variant has a REVEL score of 0.564, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function.

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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