Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778921 | SCV000915334 | uncertain significance | Factor XII deficiency disease | 2017-04-27 | criteria provided, single submitter | clinical testing | The F12 c.158A>G (p.Tyr53Cys) missense variant, also known as the factor XII Tenri variant, has been reported in one study in which it is found in one consanguineous family (Kondo et al. 1999). Kondo et al. (1999) identified the p.Tyr53Cys variant in a homozygous state in one asymptomatic individual with low but detectable blood antigen and activity levels of factor XII (3% of wild type). The variant was also found in a heterozygous state in the proband's unaffected consanguineous parents and sister who all showed reduced blood antigen and activity levels (35% of wild type). Functional studies showed that the variant protein was extensively degraded intracellularly in the endoplasmic reticulum and that a small amount of factor XII Tenri that forms a disulphide-linked heterodimer with alpha1-microglobulin is secreted into the blood stream. Control data are unavailable for this variant, which is not reported in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium or the Genome Aggregation Database. The evidence for this variant is limited. The p.Tyr53Cys variant is classified as unknown significance, but suspicious for pathogenicity for factor XII deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Illumina Laboratory Services, |
RCV001158012 | SCV001319625 | uncertain significance | Hereditary angioedema type 3 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| OMIM | RCV000778921 | SCV000021377 | pathogenic | Factor XII deficiency disease | 1999-06-15 | no assertion criteria provided | literature only |