Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Service de Biochimie Médicale et Biologie Moléculaire, |
RCV001003360 | SCV001156232 | likely pathogenic | Aicardi-Goutieres syndrome 7 | 2020-02-03 | criteria provided, single submitter | clinical testing | Variation p.(Arg799Leu) is absent from gnomAD. Two substitutions affecting the same amino-acid change is described with functional studies (Rice , 2014) indicating a "gain of function". There are 11 pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, M-CAP, MVP, MutationAssessor, MutationTaster, PrimateAI, REVEL and SIFT vs no benign predictions. |
| Invitae | RCV002551703 | SCV003255285 | pathogenic | Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 | 2023-08-10 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Aicardi–Goutières syndrome (PMID: 31898846). In at least one individual the variant was observed to be de novo. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 779 of the IFIH1 protein (p.Arg779Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in at least one individual who was not affected with IFIH1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 812532). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IFIH1 protein function. This variant disrupts the p.Arg779 amino acid residue in IFIH1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31898846; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003333119 | SCV004041390 | likely pathogenic | Singleton-Merten syndrome 1 | 2023-05-08 | criteria provided, single submitter | clinical testing | |
| Laboratory of Neurogenetics and Neuroinflammation, |
RCV001003360 | SCV001161473 | pathogenic | Aicardi-Goutieres syndrome 7 | 2019-06-11 | no assertion criteria provided | clinical testing |