Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001168451 | SCV001331042 | uncertain significance | Hereditary factor VIII deficiency disease | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
ARUP Laboratories, |
RCV001168451 | SCV002048819 | likely pathogenic | Hereditary factor VIII deficiency disease | 2021-07-12 | criteria provided, single submitter | clinical testing | The F8 c.6929C>T; p.Thr2310Ile variant (rs373079141) is reported in the literature in multiple individuals affected with mild hemophilia A (F8 database and references therein, Janczar 2020, Miller 2012). This variant is also reported in ClinVar (Variation ID: 914337). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 2310 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.642). Based on available information, this variant is considered to be likely pathogenic. References: Link to Factor VIII database: https://f8-db.eahad.org/index.php Janczar S et al. Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland. Thromb Res. 2020 Sep;193:9-14. PMID: 32497951. Miller CH et al. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity. Haemophilia. 2012 May;18(3):375-82. PMID: 22103590. |