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.1359del (p.Ser454fs)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA645372549

435427 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4f963577-be8f-47ce-b8cb-f11430e17e16

Approved on: 2025-07-24

Published on: 2025-07-24

HGVS expressions

NM_000545.8:c.1359del

NM_000545.8(HNF1A):c.1359del (p.Ser454fs)

NC_000012.12:g.120997523del

CM000674.2:g.120997523del

NC_000012.11:g.121435326del

CM000674.1:g.121435326del

NC_000012.10:g.119919709del

NG_011731.2:g.23778del

ENST00000560968.6:c.*106del

ENST00000257555.11:c.1359del

ENST00000257555.10:c.1359del

ENST00000400024.6:c.1359del

ENST00000402929.5:n.2225del

ENST00000535955.5:n.75del

ENST00000538626.2:n.223del

ENST00000538646.5:c.*335del

ENST00000540108.1:c.*799del

ENST00000541395.5:c.1359del

ENST00000541924.5:c.*373del

ENST00000543255.1:n.403del

ENST00000543427.5:c.822del

ENST00000544413.2:c.1359del

ENST00000544574.5:c.*122del

ENST00000560968.5:c.1176del

ENST00000615446.4:c.147del

ENST00000617366.4:c.587-111del

NM_000545.5:c.1359del

NM_000545.6:c.1359del

NM_001306179.1:c.1359del

NM_001306179.2:c.1359del

Likely Pathogenic

PVS1 PM2_Supporting

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 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.1359del variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 454 (NM_000545.8), adding 3 novel amino acids before encountering a stop codon (p.(Ser454AlafsTer3)). This variant, located in biologically-relevant exon 7 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). Also, this variant is absent from gnomAD v2.1.1 and v4.1.0 (PM2_Supporting). This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (internal lab contributors). In summary, c.1359del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 3.0.0, approved 6/30/2025): PVS1, PM2_Supporting.

PVS1

This variant, located in biologically-relevant exon 7 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v4.1.0 (PM2_Supporting).

PP4

This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (internal lab contributors).

Curation History

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