Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757258 | SCV000885408 | uncertain significance | not provided | 2017-12-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702393 | SCV005204402 | likely pathogenic | Hereditary factor IX deficiency disease | 2024-06-26 | criteria provided, single submitter | clinical testing | Variant summary: F9 c.196G>A (p.Glu66Lys) results in a conservative amino acid change located in the Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294) of 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 183027 control chromosomes. c.196G>A has been reported in the literature and the EAHAD database in an unknown zygosity in at least 2 individuals affected with Factor IX Deficiency (Hemophilia B) (example, Johnsen_2017, NO_PMID). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Additionally, 2 different missense variants at this codon were found to be pathogenic by our laboratory (p.Glu66Val, p.Glu66Asp) based on reported individuals affected with hemophilia B (PMID: 34880139, 34880139, 22639855, 7937052). This suggests the p.Glu66 amino acid residue is likely critical for protein function. The following publications have been ascertained in the context of this evaluation (PMID: 29296726, NO_PMID). ClinVar contains an entry for this variant (Variation ID: 618643). Based on the evidence outlined above, the variant was classified as likely pathogenic. |