ClinVar

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly368 amino acid residue in F11. Other variant(s) that disrupt this residue have been observed in individuals with F11-related conditions (PMID: 14717969, 20523169, 33751533), which suggests that this may be a clinically significant amino acid residue. This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 368 of the F11 protein (p.Gly368Ala). This variant is present in population databases (rs748926718, gnomAD 0.0009%). This missense change has been observed in individual(s) with factor XI deficiency (PMID: 14717969). This variant is also known as G350A. ClinVar contains an entry for this variant (Variation ID: 551619). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F11 protein function.