Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001386474 | SCV001586707 | pathogenic | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the F11 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with factor XI deficiency (PMID: 16835901, 29178608). ClinVar contains an entry for this variant (Variation ID: 1073465). Studies have shown that disruption of this splice site results in skipping of exon 4 and introduces a new termination codon (PMID: 29178608). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003898366 | SCV004712486 | pathogenic | F11-related condition | 2024-02-15 | criteria provided, single submitter | clinical testing | The F11 c.325+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in heterozygous state in one individual or in compound heterozygous state an two individuals with Factor XI deficiency (Table 2, Mitchell et al. 2006. PubMed ID: 16835901; Rimoldi et al. 2017. PubMed ID: 29178608). In vitro splicing assays also suggest this variant impacts splicing (Rimoldi et al. 2017. PubMed ID: 29178608). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Variants that disrupt the consensus splice donor site in F11 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Natera, |
RCV001826169 | SCV002082931 | pathogenic | Plasma factor XI deficiency | 2021-04-27 | no assertion criteria provided | clinical testing |