Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825507 | SCV000966814 | likely pathogenic | Hereditary factor VIII deficiency disease | 2017-05-04 | criteria provided, single submitter | clinical testing | The p.Phe328Leu (NM_000132.3 c.984T>G) (legacy name p.Phe309Leu) variant in F8 h as been reported in 2 (presumably hemizygous male) individuals and 2 known hemiz ygous males with Hemophilia A and related diseases (prolonged bleed after injury ) (Green 2008, Nair 2010, Pinto 2016), and was absent from large population stud ies. Computational prediction tools and conservation analysis suggest that the p .Phe328Leu variant may impact the protein, though this information is not predic tive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the p.Phe328Leu varia nt is likely pathogenic based on its occurrence in multiple affected individuals and absence from controls. |
| Genetics and Molecular Pathology, |
RCV000825507 | SCV002761494 | likely pathogenic | Hereditary factor VIII deficiency disease | 2021-01-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000825507 | SCV005205192 | likely pathogenic | Hereditary factor VIII deficiency disease | 2024-06-14 | criteria provided, single submitter | clinical testing | Variant summary: F8 c.984T>G (p.Phe328Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183036 control chromosomes. c.984T>G has been reported in the literature in individuals affected with Factor VIII Deficiency (Hemophilia A) (e.g. Nair_2015, Pinto_2016, Green_2008, Nance_2013). These data indicate that the variant is likely to be associated with disease. This variant is also known as F309L. The following publications have been ascertained in the context of this evaluation (PMID: 18691168, 25550078, 23711294, 26897466). ClinVar contains an entry for this variant (Variation ID: 666959). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV004792545 | SCV005411532 | uncertain significance | not provided | 2024-07-16 | criteria provided, single submitter | clinical testing | PP3, PM1_supporting, PM2, PS4_moderate |