ClinVar Miner

Submissions for variant NM_000133.4(F9):c.1106T>C (p.Leu369Pro)

dbSNP: rs1603267393
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851659 SCV000899427 likely pathogenic Hereditary factor VIII deficiency disease 2019-02-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001378168 SCV001575679 likely pathogenic Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect 2020-05-23 criteria provided, single submitter clinical testing This variant disrupts the p.Leu369 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 15921378, 17014892), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with hemophilia B (PMID: 19699296, 27865967). This variant is also referred to as p.Leu323Pro in the literature. ClinVar contains an entry for this variant (Variation ID: 626973). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 369 of the F9 protein (p.Leu369Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.

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