Evidence Repository
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
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_001306179.2:c.865C>T

CA386966635

1315612 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8e113349-d440-4f07-8182-c050d43a54bf

HGVS expressions

NM_001306179.2:c.865C>T
NC_000012.12:g.120994315C>T
CM000674.2:g.120994315C>T
NC_000012.11:g.121432118C>T
CM000674.1:g.121432118C>T
NC_000012.10:g.119916501C>T
NG_011731.2:g.20570C>T
ENST00000257555.11:c.865C>T
ENST00000257555.10:c.865C>T
ENST00000400024.6:c.865C>T
ENST00000402929.5:n.1000C>T
ENST00000535955.5:n.43-3176C>T
ENST00000538626.2:n.191-3176C>T
ENST00000538646.5:c.678C>T
ENST00000540108.1:c.*305C>T
ENST00000541395.5:c.865C>T
ENST00000541924.5:c.713+609C>T
ENST00000543427.5:c.633+689C>T
ENST00000544413.2:c.865C>T
ENST00000544574.5:c.73-2302C>T
ENST00000560968.5:n.893+115C>T
ENST00000615446.4:c.-257-1947C>T
ENST00000617366.4:c.586+736C>T
NM_000545.5:c.865C>T
NM_000545.6:c.865C>T
NM_001306179.1:c.865C>T
NM_000545.8:c.865C>T
NM_000545.8(HNF1A):c.865C>T (p.Pro289Ser)

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 2
PM5 PP4

Evidence Links 0

Expert Panel

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.865C>T variant in the e.g. HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to serine at codon 289 (p.(Pro289Ser)) of NM_000545.8. This variant is also absent from 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 age of diagnosis over 35; therefore, PP4 cannot be applied (internal lab contributors). Two other missense variants, c.866C>A (p.Pro289His) and c.866C>G (p.Pro289Arg), have been classified as VUS by the ClinGen MDEP; therefore PM5 will not be applied. In summary, c.865C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM2_Supporting.
Met criteria codes
PM2_Supporting
Absent from gnomAD v2.1.1.
Not Met criteria codes
PM5
Two other missense variants, c.866C>A (p.Pro289His) and c.866C>G (p.Pro289Arg), have been classified as VUS by the ClinGen MDEP.
PP4
This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to age of diagnosis over 35 (internal lab contributors).
Approved on: 2022-04-15
Published on: 2022-07-12
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