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_000545.6(HNF1A):c.1359del (p.Ser454fs)

CA645372549

435427 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

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

HGVS expressions

NM_000545.6:c.1359del

NM_000545.6(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

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:n.1176del

ENST00000615446.4:c.147del

ENST00000617366.4:c.587-111del

NM_000545.5:c.1359del

NM_001306179.1:c.1359del

NM_000545.8:c.1359del

NM_001306179.2:c.1359del

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

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PVS1 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 Version 1

PDF

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 (PM2_Supporting). 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 1.0, approved 6/4/2021): PVS1, PM2_Supporting

PVS1

This variant is predicted to cause loss of function by resulting in nonsense mediated decay of a biologically relevant transcript.

PM2_Supporting

This variant is absent from gnomAD.

Approved on: 2021-12-31

Published on: 2022-07-11

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