Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| NIHR Bioresource Rare Diseases, |
RCV000852053 | SCV000899562 | pathogenic | Hereditary factor IX deficiency disease | 2019-02-01 | criteria provided, single submitter | research | |
| Illumina Laboratory Services, |
RCV001249714 | SCV001423739 | likely pathogenic | Hereditary factor VIII deficiency disease | 2019-10-08 | criteria provided, single submitter | clinical testing | The F8 c.1804C>G (p.Arg602Gly) missense variant that has been reported in at least two studies and is identified in a hemizygous state in at least eight individuals with mild hemophilia A (Bowyer et al. 2013; Beskorovainaya et al. 2019). Control data are unavailable for this variant, which is not found in in the Genome Aggregation Database despite good sequence coverage, so the variant is presumed to be rare. Based on the prevalence of the variant in affected individuals compared to controls, absence from population frequency databases, and location in a functional domain in a variant hotspot, the p.Arg602Gly variant is classified as likely pathogenic for hemophilia A. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001249714 | SCV004223631 | pathogenic | Hereditary factor VIII deficiency disease | 2023-11-10 | criteria provided, single submitter | clinical testing | Variant summary: F8 c.1804C>G (p.Arg602Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183429 control chromosomes. c.1804C>G has been reported in the literature in multiple individuals affected with mild Factor VIII Deficiency (Hemophilia A) (example, Hill_2005, Green_2008, Miller_2012, Eckhardt_2013, Downes_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31064749, 23926300, 18691168, 15810915, 22103590). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |