ClinVar Miner

Submissions for variant NM_000128.3(F11):c.1724C>T (p.Ser575Leu) (rs281875250)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000454166 SCV000538024 likely pathogenic Hereditary factor XI deficiency disease 2016-03-30 criteria provided, single submitter clinical testing The c.1724C>T (p.Ser575Leu) missense variant in the F11 gene has been previously reported in three unrelated individuals affected with CRM+ Factor XI deficiency. Consistent with the CRM+ type Factor XI deficiency, these individuals had reduced coagulation activity but normal antigen levels (FXI:Ag = 60-86 UI/dL) indicating there was normal level of protein present in the plasma, but reduced enzyme function (Guéguen et al., 2012). The individual who was homozygous for this variant had lower coagulation activity (FXI C:1 UI/dL) compared with the two individuals who were heterozygous for this variant (FXI C: 28 UI/dL and 38 UI/dL respectively; normal range 70-15 IU/dL). The c.1724C>T (p.Ser575Leu) variant is located in the active site of the FXI protein, which would be predicted to inhibit the serine protease function of the protein. This variant is absent from the population databases (Exome Sequencing Project; 1000 Genomes; ExAC). Multiple in silico algorithms predict a deleterious effect (GERP = 5.05; CADD = 16.48; PolyPhen = 1.0; SIFT = 0). Therefore, this collective evidence supports the classification of the c.1724C>T (p.Ser575Leu) as a Likely pathogenic variant for Factor XI Deficiency.
UniProtKB/Swiss-Prot RCV000059019 SCV000090540 not provided not provided no assertion provided not provided

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