Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV003104145 | SCV002058061 | pathogenic | not provided | 2023-05-02 | criteria provided, single submitter | clinical testing | The F8 c.4379dupA; p.Asn1460LysfsTer2 variant (rs387906455), also known as p.Asn1442LysfsTer2, is reported in numerous individuals with hemophilia A (see Factor VIII database, Lu 2018). In vitro functional analyses demonstrate that individuals with this variant have factor VIII activity of <1-8%. It is reported in one allele in the Genome Aggregation Database, but is considered a low confidence variant in that database. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to Factor VIII database: https://f8-db.eahad.org/index.php Lu Y et al. Spectrum and origin of mutations in sporadic cases of haemophilia A in China. Haemophilia. 2018 Mar;24(2):291-298. PMID: 29381227. |
| Fulgent Genetics, |
RCV002503301 | SCV002810386 | pathogenic | Hereditary factor VIII deficiency disease; Thrombophilia, X-linked, due to factor 8 defect | 2021-11-06 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV001807852 | SCV004100372 | likely pathogenic | Hereditary factor VIII deficiency disease | criteria provided, single submitter | clinical testing | The frameshift duplication p.N1460Kfs*2 in F8 (NM_000132.4) has been reported in multiple affected indviduals (AbdulGhafar A et al,Hwang SH et al). It has been submitted to ClinVar as PathogenicAlthough the variant is present at 0.0006% in gnomAD Exomes, it has the flag "Failed Random Forest" and may not represent the true population frequency. The p.N1460Kfs*2 variant is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation.Loss of function variants have been reported previously as disease causing. For these reasons, this variant has been classified as Likely Pathogenic | |
| Gene |
RCV003104145 | SCV005078983 | pathogenic | not provided | 2023-11-15 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also denoted as c.4372insA due to alternative nomenclature; This variant is associated with the following publications: (PMID: 1908096, 7794769, 11102988, 8054459, 10519986, 19473408, 19686262, 18388498, 35014236, 20838461, 12325022, 12871415, 9603440, 10896236, 11298607, 11843836, 11857744, 12195713, 16601827, 18403393, 19719548, 20028422, 20800587, 29381227, 18691168, 33245802, 32497951, 32897612) |
| Juno Genomics, |
RCV002503301 | SCV005417583 | pathogenic | Hereditary factor VIII deficiency disease; Thrombophilia, X-linked, due to factor 8 defect | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PS4_Supporting+PP4 | |
| OMIM | RCV001807852 | SCV000031200 | pathogenic | Hereditary factor VIII deficiency disease | 1991-08-15 | no assertion criteria provided | literature only |