Variant: NM_000545.8(HNF1A):c.313dup (p.Glu105fs)

CA214298

36817 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: cc3f16f5-5674-402d-a312-71bc457dbb8a

Approved on: 2025-06-09

Published on: 2025-06-09

HGVS expressions

NM_000545.8:c.313dup
NM_000545.8(HNF1A):c.313dup (p.Glu105fs)
NC_000012.12:g.120979081dup
CM000674.2:g.120979081dup
NC_000012.11:g.121416884dup
CM000674.1:g.121416884dup
NC_000012.10:g.119901267dup
NG_011731.2:g.5336dup
ENST00000560968.6:c.313dup
ENST00000257555.11:c.313dup
ENST00000257555.10:c.313dup
ENST00000400024.6:c.313dup
ENST00000402929.5:n.448dup
ENST00000535955.5:n.42+389dup
ENST00000538626.2:n.190+241dup
ENST00000538646.5:c.313dup
ENST00000540108.1:c.313dup
ENST00000541395.5:c.313dup
ENST00000541924.5:c.313dup
ENST00000543427.5:c.313dup
ENST00000544413.2:c.313dup
ENST00000544574.5:c.72+241dup
ENST00000560968.5:c.456dup
ENST00000615446.4:c.-258+370dup
ENST00000617366.4:c.313dup
NM_000545.5:c.313dup
NM_000545.6:c.313dup
NM_001306179.1:c.313dup
NM_001306179.2:c.313dup

Likely Pathogenic

• Met criteria codes: PVS1_Strong PM2_Supporting

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 2.1.0

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.313dup variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 105 (NM_000545.8), adding 83 novel amino acids before encountering a stop codon (p.(Glu105GlyfsTer83)). This variant, located in biologically-relevant exon 1 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). Additionally, this variant is absent from gnomAD v2.1.1 and v4.1.0 (PM2_Supporting). In summary, c.313dup meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/23): PVS1, PM2_Supporting.

Met criteria codes

• PVS1_Strong: This variant, located in biologically-relevant exon 1 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).