Submissions for variant NM_000132.4(F8):c.412del (p.Ser138fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003486495	SCV004241318	pathogenic	Hereditary factor VIII deficiency disease	2023-12-19	criteria provided, single submitter	clinical testing	Variant summary: F8 c.412delA (p.Ser138ValfsX23) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 182879 control chromosomes. c.412delA has been reported in the literature in at least one individual from a cohort containing hemophilia affected individuals, genetic carriers, or those at risk due to family history (e.g. Johnsen_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Factor VIII Deficiency (Hemophilia A). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 35770352). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.