ClinVar Miner

Submissions for variant NM_000132.4(F8):c.5453dup (p.Ala1819fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018216 SCV004848811 likely pathogenic Hereditary factor VIII deficiency disease 2022-11-03 criteria provided, single submitter clinical testing The p.Ala1819SerfsX4 variant in F8 has not been reported in individuals with hemophilia and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1819 and leads to a premature termination codon 4 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the F8 gene is an established disease mechanism in X-linked hemophilia A. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for X-linked hemophilia A. ACMG/AMP Criteria applied: PM2_Supporting, PVS1.

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