ClinVar

Description

Variant summary: F8 c.1601T>C (p.Val534Ala) results in a non-conservative amino acid change located in the Multicopper oxidase-like, N-terminal domain (IPR011707) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183421 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1601T>C has been reported in the literature as as a mild variant listed in the PedNet Registry of individuals affected with Factor VIII Deficiency (Hemophilia A) (Andersson_2020). These data do not allow any conclusion about variant significance. To our knowledge, no primary experimental evidence demonstrating an impact on protein function has been reported although the publication cited above lists reports a FVIII activity of 7% and a clinical significance of a mild class 5 category (Pathogenic). The following publication have been ascertained in the context of this evaluation (PMID: 32935414). ClinVar contains an entry for this variant (Variation ID: 439681). Based on the evidence outlined above, the variant was classified as uncertain significance.