Submissions for variant NM_000128.4(F11):c.1060G>A (p.Gly354Arg)

gnomAD frequency: 0.00001  dbSNP: rs777714867

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002002875	SCV002270808	pathogenic	not provided	2023-04-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects F11 function (PMID: 21718436). 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. ClinVar contains an entry for this variant (Variation ID: 1482231). This variant is also known as p.Gly336Arg. This missense change has been observed in individuals with autosomal recessive factor XI deficiency (PMID: 14717969, 21718436, 24112640). This variant is present in population databases (rs777714867, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 354 of the F11 protein (p.Gly354Arg).
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002280909	SCV002569288	likely pathogenic	Hereditary factor XI deficiency disease		criteria provided, single submitter	clinical testing