Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Lifecell International Pvt. |
RCV003229495 | SCV003926472 | likely pathogenic | Aicardi-Goutieres syndrome 7 | criteria provided, single submitter | clinical testing | A Heterozygous Splice site donor variant c.2304+1G>T in Exon 11 of the IFIH1 gene that results in the amino acid substitution was identified. The observed variant has a minimum allele frequency of 0.00000% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. Based on the above evidence this variant has been classified as according to the ACMG guidelines. | |
Labcorp Genetics |
RCV003779831 | SCV004573810 | uncertain significance | Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 | 2023-02-10 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This variant has not been reported in the literature in individuals affected with IFIH1-related conditions. This sequence change affects a donor splice site in intron 11 of the IFIH1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in IFIH1 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.0009%). |