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_001306179.2:c.1481C>T

CA386970356

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: adf7820f-b316-49c1-adce-6b4f7f06c07d

HGVS expressions

NM_001306179.2:c.1481C>T

Uncertain Significance

PM2_Supporting PP3

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 Version 1.2

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1481C>T variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of alanine to valine at codon 494 (p.(Ala494Val)) of NM_000545.8. This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.8439, which is greater the MDEP VCEP threshold of 0.70 (PP3). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information (internal lab contributor). In summary, the c.1481C>T variant meets the criteria to be classified as a VUS for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 1/11/2023): PP3, PM2_Supporting.

PM2_Supporting

This variant is absent in gnomAD v2.1.1 (PM2_Supporting).

PP3

This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.8439, which is greater the MDEP VCEP threshold of 0.70 (PP3).

PP4

This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information (internal lab contributor).

Approved on: 2023-07-30

Published on: 2023-07-30

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