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.1A>C

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA386951959

1342948 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 49ffa87c-44f9-4d04-bfeb-fc924bca0990

Approved on: 2022-03-04

Published on: 2022-07-11

HGVS expressions

NM_001306179.2:c.1A>C

NC_000012.12:g.120978769A>C

CM000674.2:g.120978769A>C

NC_000012.11:g.121416572A>C

CM000674.1:g.121416572A>C

NC_000012.10:g.119900955A>C

NG_011731.2:g.5024A>C

ENST00000257555.11:c.1A>C

ENST00000257555.10:c.1A>C

ENST00000400024.6:c.1A>C

ENST00000402929.5:n.136A>C

ENST00000535955.5:n.42+77A>C

ENST00000538626.2:n.119A>C

ENST00000538646.5:c.1A>C

ENST00000540108.1:c.1A>C

ENST00000541395.5:c.1A>C

ENST00000541924.5:c.1A>C

ENST00000543427.5:c.1A>C

ENST00000544413.2:c.1A>C

ENST00000544574.5:c.1A>C

ENST00000560968.5:n.144A>C

ENST00000615446.4:c.-258+58A>C

ENST00000617366.4:c.1A>C

NM_000545.5:c.1A>C

NM_000545.6:c.1A>C

NM_001306179.1:c.1A>C

NM_000545.8:c.1A>C

NM_000545.8(HNF1A):c.1A>C (p.Met1Leu)

Likely Pathogenic

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

PM2_Supporting PVS1

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 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1A>C variant in the HNF1 homeobox A gene, HNF1A, results in the loss of the initiation codon (p.Met1?) of NM_000545.8. By altering the start codon of the coding sequence, this variant is predicted to cause a truncated or absent protein in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1A>C meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PVS1, PM2_Supporting

PM2_Supporting

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

PVS1

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

Curation History

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