ClinVar Miner

Submissions for variant NM_022168.4(IFIH1):c.2459G>A (p.Arg820His)

gnomAD frequency: 0.00024  dbSNP: rs74162087
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489685 SCV000577058 uncertain significance not provided 2017-04-11 criteria provided, single submitter clinical testing The R820H variant in the IFIH1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R820H variant is observed in 5/10196 (0.049%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016). The R820H variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R822Q, R824K) have been reported in association with IFIH1-related phenotypes, including Singleton-Merten syndrome and Aicardi-Goutieres syndrome, supporting the functional importance of this region of the protein (Bursztejn et al., 2015; Rutsch et al., 2015; Pettersson et al., 2017; Crow et al., 2015). We interpret R820H as a variant of uncertain significance
Labcorp Genetics (formerly Invitae), Labcorp RCV000549571 SCV000655029 likely benign Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2024-01-25 criteria provided, single submitter clinical testing
Institute of Human Genetics, University Hospital Muenster RCV002222185 SCV002499710 uncertain significance Singleton-Merten syndrome 1 2022-03-29 criteria provided, single submitter clinical testing ACMG categories: PM1,PM2,PP3
PreventionGenetics, part of Exact Sciences RCV003409674 SCV004112817 uncertain significance IFIH1-related disorder 2022-10-05 criteria provided, single submitter clinical testing The IFIH1 c.2459G>A variant is predicted to result in the amino acid substitution p.Arg820His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-163128893-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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