Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000428343 | SCV000536670 | uncertain significance | not provided | 2017-02-07 | criteria provided, single submitter | clinical testing | The I410T variant in the IFIH1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I410T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I410T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I410T as a variant of uncertain significance. |
Labcorp Genetics |
RCV002298591 | SCV002593539 | uncertain significance | Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 | 2022-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 410 of the IFIH1 protein (p.Ile410Thr). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 393285). This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. This variant is not present in population databases (gnomAD no frequency). |