Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001111144 | SCV001268660 | uncertain significance | Factor VII deficiency | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526802 | SCV005039124 | uncertain significance | not specified | 2024-03-25 | criteria provided, single submitter | clinical testing | Variant summary: F7 c.1006G>A (p.Val336Met) results in a 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 1.6e-05 in 249662 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1006G>A has been reported in the literature in an individual affected with Congenital factor VII deficiency (Lou_2023). These data do not allow any conclusion about variant significance. This publication also reports experimental evidence evaluating an impact on protein function, finding that the variant does not result in a significant change in FVII:Ag levels but does significantly inhibit procoagulant activity (FVIII:C). The following publication has been ascertained in the context of this evaluation (PMID: 36951360). ClinVar contains an entry for this variant (Variation ID: 881853). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |