Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004790044 | SCV005399302 | pathogenic | Hereditary factor XI deficiency disease | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene (Decipher). (N) 0104 - Dominant Negative is a mechanism of disease for this gene. Missense variants have been reported to cause both loss of function (PMID:25681615) and dominant negative (PMID:15026311) consequence on protein function. (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Dominant negative missense contribute most dominantly-inherited variants (PMID:15026311), however rare symptomatic patients with heterozygous NMD-predicted variants have also been reported (OMIM). (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein. This variant is in exon 7 of 15 of the F11 gene. (P) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 (1 heterozygote, 0 homozygotes). (P) 0701 - Comparable variants also predicted to result in NMD, have very strong previous evidence for pathogenicity in patients with excessive bleeding (Decipher, OMIM, PMID:25681615). (P) 0803 - Low previous evidence of pathogenicity in a single individual with FXI deficiency and a missense in trans (PMID:18446632). (P) 0905 - No segregation evidence has been identified for this variant in the literature. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 – Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |