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_000545.8(HNF1A):c.1819dup (p.Gln607fs)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA645509328

438709 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5f7dfcb6-9545-4f1c-99d8-57f30279f4a3

Approved on: 2025-10-03

Published on: 2025-10-03

HGVS expressions

NM_000545.8:c.1819dup

NM_000545.8(HNF1A):c.1819dup (p.Gln607fs)

NC_000012.12:g.121001115dup

CM000674.2:g.121001115dup

NC_000012.11:g.121438918dup

CM000674.1:g.121438918dup

NC_000012.10:g.119923301dup

NG_011731.2:g.27370dup

ENST00000560968.6:c.*566dup

ENST00000257555.11:c.1819dup

ENST00000257555.10:c.1819dup

ENST00000288757.7:c.*3039dup

ENST00000540108.1:c.*1259dup

ENST00000541395.5:c.1912dup

ENST00000543427.5:c.1282dup

ENST00000544413.2:c.1840dup

ENST00000560968.5:c.1636dup

ENST00000615446.4:c.607dup

ENST00000617366.4:c.*228dup

NM_000545.5:c.1819dup

NM_000545.6:c.1819dup

NM_001306179.1:c.1840dup

NM_001286191.2:c.*3039dup

NM_001286196.2:c.*3039dup

NM_001306179.2:c.1840dup

NM_022895.3:c.*3039dup

Uncertain Significance

PVS1_Strong PM2_Supporting

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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1819dup variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 607, adding 42 novel amino acids before encountering a stop codon (p.(Gln607ProfsTer42) of NM_000545.8. While this variant, located in exon 10 of 10, is not predicted to result in nonsense mediated decay of the transcript, it will significantly disrupt the transactivation domain of the protein and add 16 additional amino acids to the end of the protein (PVS1_Strong). Additionally, this variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, c.1819dup 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 3.0.0, approved 6/30/2025): PVS1_Strong, PM2_Supporting.

PVS1_Strong

While this variant is located 5' of c.1854 in exon 10 of 10 and is not predicted to result in nonsense mediated decay of the transcript, it will significantly disrupt the transactivation domain of the protein and add 16 novel amino acids to the end of the protein.

PM2_Supporting

Absent from gnomAD v4.1.0.

Curation History

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