Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV003434309 | SCV004161309 | likely benign | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | GIMAP1-GIMAP5: BP4 |
| Neuberg Centre For Genomic Medicine, |
RCV001548746 | SCV004175809 | pathogenic | Portal hypertension, noncirrhotic, 2 | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense c.611T>C (p.Leu204Pro) in GIMAP5 gene has been reported previously in homozygous state in individuals affected with GIMAP5-associated hypertension (Patterson et al. 2018; Drzewiecki et al. 2021). Experimental studies demonstrated an undetectable protein expression of both GIMAP5 isoforms for this variant (Patterson et al. 2018). This variant is reported with an allele frequency of 0.2% in the gnomAD exomes database. This variant has been reported to the ClinVar database as Likely Pathogenic / Pathogenic. The amino acid change p.Leu204Pro in GIMAP5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Leu at position 204 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001548746 | SCV004804153 | likely pathogenic | Portal hypertension, noncirrhotic, 2 | 2024-01-04 | criteria provided, single submitter | clinical testing | Variant summary: GIMAP5 c.611T>C (p.Leu204Pro) results in a non-conservative amino acid change located in the AIG1-type guanine nucleotide-binding (G) domain (IPR006703) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.002 in 251010 control chromosomes in the gnomAD database, including 1 homozygotes. c.611T>C has been reported in the literature in a homozygous individuals affected with GIMAP5-associated hypertension. T cells isolated from this patient had complete loss of GIMAP5 protein expression, reduced T cell proliferation which was restored upon pharmacological targeting of GSK3. (example: Patterson_2018, and Drewieck_GIMAP5_JEM_2021). These data indicate that the variant may be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 33956074, 29382851, 35753512).Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic (n=2) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV001548746 | SCV001768715 | pathogenic | Portal hypertension, noncirrhotic, 2 | 2021-08-02 | no assertion criteria provided | literature only | |
| Yale Center for Mendelian Genomics, |
RCV001849525 | SCV002107006 | likely pathogenic | Portal hypertension | 2021-05-06 | no assertion criteria provided | literature only |