Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671578 | SCV000796566 | uncertain significance | Hereditary factor XI deficiency disease | 2017-12-28 | criteria provided, single submitter | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV000671578 | SCV000899750 | likely pathogenic | Hereditary factor XI deficiency disease | 2019-02-01 | criteria provided, single submitter | research | |
Center for Genomic Medicine, |
RCV000671578 | SCV004809957 | likely pathogenic | Hereditary factor XI deficiency disease | 2024-04-04 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000671578 | SCV004848698 | likely pathogenic | Hereditary factor XI deficiency disease | 2022-06-30 | criteria provided, single submitter | clinical testing | The p.Thr150Met variant in F11 has been reported in one heterozygous individual and one compound heterozygous individual both with Factor XI defieciency (Mitchell 2006 PMID: 16835901, Saunders 2009 PMID: 19652879), and Factor XI assays for both individuals showed dimished activity. The variant has been in 0.02% (1/4828) South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/); however this frequency is low enough to be consistent with a carrier frequency for pathogenic F11 variants. Computational prediction tools and conservation analysis suggest that the p.Thr150Met variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Factor XI deficiency. ACMG/AMP Criteria applied: PS3, PM3, PP3, PS4_Supporting. |