NM_001306179.2:c.98C>T

CA244520729

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: af2a9d25-bd60-40e7-b8ca-ee284a1fb79c

HGVS expressions

NM_001306179.2:c.98C>T
NC_000012.12:g.120978866C>T
CM000674.2:g.120978866C>T
NC_000012.11:g.121416669C>T
CM000674.1:g.121416669C>T
NC_000012.10:g.119901052C>T
NG_011731.2:g.5121C>T
ENST00000257555.11:c.98C>T
ENST00000257555.10:c.98C>T
ENST00000400024.6:c.98C>T
ENST00000402929.5:n.233C>T
ENST00000535955.5:n.42+174C>T
ENST00000538626.2:n.190+26C>T
ENST00000538646.5:c.98C>T
ENST00000540108.1:c.98C>T
ENST00000541395.5:c.98C>T
ENST00000541924.5:c.98C>T
ENST00000543427.5:c.98C>T
ENST00000544413.2:c.98C>T
ENST00000544574.5:c.72+26C>T
ENST00000560968.5:n.241C>T
ENST00000615446.4:c.-258+155C>T
ENST00000617366.4:c.98C>T
NM_000545.5:c.98C>T
NM_000545.6:c.98C>T
NM_001306179.1:c.98C>T
NM_000545.8:c.98C>T

Likely Pathogenic

• Met criteria codes: PS4 PM2_Supporting PP4

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

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.98C>T variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to leucine at codon 33(p.(Pro33Leu)) of NM_000545.8. This variant was identified in at least one individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%,, and response to sulfonylurea) (PP4; internal lab contributors). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). Lastly, this variant was identified in seven unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4; PMID 32238361, internal lab contributors). In summary, c.98C>T 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 9/30/21): PM2_Supporting, PS4_Strong, PP4.

Met criteria codes

• PS4: This variant was identified in seven unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4; PMID: 3223838361, internal lab contributors).
• PM2_Supporting: Absent from gnomAD
• PP4: This variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, sulfonylurea-responsive)(internal lab contributors).

Approved on: 2022-04-02

Published on: 2022-07-12