Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000743 | SCV001157790 | uncertain significance | Hereditary factor VIII deficiency disease | 2018-08-03 | criteria provided, single submitter | clinical testing | The F8 c.1231G>A; p.Asp411Asn variant, to our knowledge, is not described in the medical literature or in gene-specific databases. It is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The aspartic acid at codon 411 is moderately conserved, but computational algorithms (PolyPhen-2: possibly damaging, SIFT: tolerated) are inconclusive on the effect of this variant on protein structure/function. A different variant at this codon (c.1232A>G; p.Asp411Gly) has been described in individuals with mild hemophilia A and is considered pathogenic (see link to FVIII database). However, due to lack of clinical and functional data regarding the p.Asp411Asn variant, its clinical significance cannot be determined with certainty. REFERENCES FVIII database: http://www.factorviii-db.org/ |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702568 | SCV005202297 | uncertain significance | not specified | 2024-07-29 | criteria provided, single submitter | clinical testing | Variant summary: F8 c.1231G>A (p.Asp411Asn) results in a 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 182924 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1231G>A has been reported in the literature in at least one individual affected with Factor VIII Deficiency (Hemophilia A) (Johnsen_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Factor VIII Deficiency (Hemophilia A). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35770352). ClinVar contains an entry for this variant (Variation ID: 811101). Based on the evidence outlined above, the variant was classified as uncertain significance. |