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_000133.4(F9):c.1105C>T (p.Leu369Phe)

CA414445918

1512896 (ClinVar)

Gene: F9 (HGNC:2158)

Condition: hemophilia B (MONDO:0010604)

Inheritance Mode: X-linked inheritance

UUID: 8a239405-afa4-4c2e-8fa0-a217aa9becce

Approved on: 2025-08-15

Published on: 2025-08-21

HGVS expressions

NM_000133.4:c.1105C>T

NM_000133.4(F9):c.1105C>T (p.Leu369Phe)

NC_000023.11:g.139561790C>T

CM000685.2:g.139561790C>T

NC_000023.10:g.138643949C>T

CM000685.1:g.138643949C>T

NC_000023.9:g.138471615C>T

NG_007994.1:g.36055C>T

ENST00000218099.7:c.1105C>T

ENST00000643157.1:n.1723+49C>T

ENST00000218099.6:c.1105C>T

ENST00000394090.2:c.991C>T

NM_000133.3:c.1105C>T

NM_001313913.1:c.991C>T

NM_001313913.2:c.991C>T

Uncertain Significance

PP3 PS4_Moderate PM2_Supporting PM5_Supporting

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The F9 c.1105C>T, p.Leu369Phe variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting). The computational predictor REVEL gives a score of 0.928, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). This variant has been reported in 2 probands meeting phenotypic criteria for hemophilia B (PS4_Moderate; PMID: 15921378, PMID: 25929987). There is another variant at this position (p.Leu369Pro) that has been curated by the Coagulation Factor Deficiency VCEP to be likely pathogenic, meeting PM5_Supporting. In summary, this variant meets the criteria to be classified as variant of uncertain significance for hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP (version 1.0.0, released 10/5/2023): PS4_Moderate, PM2_Supporting, PP3, PM5_Supporting.

PP3

The computational predictor REVEL gives a score of 0.928, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3).

PS4_Moderate

This variant has been reported in 2 probands meeting phenotypic criteria for Hemophilia B (PS4_moderate; PMID: 15921378, PMID: 25929987).

PM2_Supporting

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

PM5_Supporting

There is a variant at this position (p.Leu369Pro) has been curated by the CFD VCEP to be likely pathogenic. There is one variant at this position (p.Leu369=) that has been curated by the CFD VCEP to be likely benign. There is also one variant (p.Leu369Val) that will not be curated due to lack of evidence.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.