Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000010910 | SCV004813205 | pathogenic | Hereditary factor VIII deficiency disease | 2024-02-20 | criteria provided, single submitter | clinical testing | Variant summary: F8 c.940A>G (p.Thr314Ala) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 183340 control chromosomes (gnomAD). c.940A>G has been reported in the literature in multiple individuals affected with Factor VIII Deficiency (Hemophilia A; e.g. Higughi_1991b, Schwaab_1995, Eckhardt_2013). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 1924291, 8547094, 23926300). ClinVar contains an entry for this variant (Variation ID: 10197). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Ce |
RCV004566717 | SCV005051204 | likely pathogenic | not provided | 2024-06-01 | criteria provided, single submitter | clinical testing | F8: PM1, PM2, PS4:Moderate |
| ARUP Laboratories, |
RCV004566717 | SCV005876853 | pathogenic | not provided | 2024-06-24 | criteria provided, single submitter | clinical testing | The F8 c.940A>G; p.Thr314Ala variant (rs137852406, ClinVar Variation ID: 10197), also known as Thr295Ala in traditional nomenclature, is reported in the literature in individuals affected with mild-moderate hemophilia A (Markoff 2009, see F8 database and references therein). This variant is only observed on one allele in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Additionally, other variants at this codon (c.941C>T, p.Thr314Ile) have been reported in individuals with moderate hemophilia A (see F8 database and references therein) and are considered to be disease causing. Computational analyses predict that this variant is deleterious (REVEL: 0.907). Based on available information, this variant is considered to be pathogenic. References: F8 databse: http://f8-db.eahad.org/index.php Markoff A et al. Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function. Haemophilia. 2009 Jul;15(4):932-41. PMID: 19473423. |
| OMIM | RCV000010910 | SCV000031137 | pathogenic | Hereditary factor VIII deficiency disease | 1991-10-01 | no assertion criteria provided | literature only |