ClinVar Miner

Submissions for variant NM_000132.3(F8):c.5815G>C (p.Ala1939Pro) (rs1603432979)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002198 SCV001160071 likely pathogenic Hereditary factor VIII deficiency disease 2018-11-09 criteria provided, single submitter clinical testing The F8 c.5815G>C; p.Ala1939Pro 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 alanine at codon 1939 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. This variant also occurs at the last nucleotide in the exon and is predicted to weaken the nearby canonical donor splice site (Alamut v.2.11). Additional variants at this position (p.Ala1939Glu, p.Ala1939Ser, and p.Ala1939Thr) have been described in individuals affected with severe hemophilia A and are considered pathogenic (see link to F8 database and references therein). Based on available information, the p.Ala1939Pro variant is considered likely pathogenic. REFERENCES Link to F8 database: http://www.factorviii-db.org/

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