Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV001508717 | SCV001715055 | likely pathogenic | not provided | 2020-12-09 | criteria provided, single submitter | clinical testing | PS3, PS4_moderate, PM1, PM2, PP1 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479334 | SCV004223564 | pathogenic | Congenital factor VII deficiency | 2023-11-09 | criteria provided, single submitter | clinical testing | Variant summary: F7 c.920G>A (p.Arg307His) results in a non-conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 248952 control chromosomes. c.920G>A, also known as p.Arg247His has been reported at a homozygous state in at-least four individuals affected with Congenital factor VII deficiency (examples, Trujillano_2017, Ohiwa_1994). Furthermore, this variant at a heterozygous state, was reported in one individual with bleeding symptoms including gum bleed, hematomas and reduced FVII levels (Herrmann_2009) and in several relatives with moderately impaired prothrombin time, reduced levels and activities of factor VII antigen (Ohiwa_1994). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in impaired secretion of the mutated factor VII (about 58% of WT) (Ohiwa_1994). The following publications have been ascertained in the context of this evaluation (PMID: 7974346, 27848944, 18976247). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Center for Genomic Medicine, |
RCV003479334 | SCV004804791 | likely pathogenic | Congenital factor VII deficiency | 2024-03-17 | criteria provided, single submitter | research | |
| OMIM | RCV001843373 | SCV000033091 | pathogenic | Factor VII deficiency | 1994-06-01 | no assertion criteria provided | literature only |