ClinVar Miner

Submissions for variant NM_000133.4(F9):c.1359G>A (p.Trp453Ter)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen RCV004577675 SCV005061653 pathogenic Hereditary factor IX deficiency disease 2024-04-26 reviewed by expert panel curation The variant c.1359G>A (p.Trp453Ter) introduces a premature stop codon in the last exon and is predicted to result in a truncated protein with more than 90% of the protein intact. This variant has been reported in at least 5 probands with severe hemophilia B, including as a de novo occurrence with assumed maternity and paternity, meeting phenotypic criteria for F9 (PMID: 36347023; PMID: 10698280; PMID: 8091381; PMID: 29296726). This variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3). In summary, this variant meets the criteria to be classified as pathogenic. ACMG/AMP criteria are applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: PVS1_moderate + PM2 supporting + PS4 + PP4_Moderate. (ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0, Released 10/5/2023).

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