ClinVar Miner

Submissions for variant NM_022168.4(IFIH1):c.1357G>C (p.Val453Leu)

gnomAD frequency: 0.00002  dbSNP: rs367921237
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001839125 SCV002099042 uncertain significance Aicardi-Goutieres syndrome 7 2021-02-19 criteria provided, single submitter clinical testing The inherited heterozygous c.1357G>C (p.Val453Leu) missense variant identified in the IFIH1 gene has not been reported in affected individual in the literature. The variant has 0.00001974 allele frequency in the gnomAD database (3 out of 151,962 heterozygous alleles, no homozygotes)suggesting it is not a common benign variant in populations represented in that database. The variant affects a conserved residue and is predicted deleterious by multiple in silico tools. Functional studies to evaluate the potential consequences of this variant have not been reported. Based on the available evidence, the inherited c.1357G>C (p.Val453Leu) variant identified in the IFIH1 gene is reported as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869851 SCV002316772 uncertain significance Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 453 of the IFIH1 protein (p.Val453Leu). This variant is present in population databases (rs367921237, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1342374). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IFIH1 protein function. 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.
Revvity Omics, Revvity RCV003132542 SCV003810013 uncertain significance not provided 2019-12-03 criteria provided, single submitter clinical testing

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