ClinVar Miner

Submissions for variant NM_022168.4(IFIH1):c.1641+1G>C (rs35337543)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000584843 SCV000693003 likely pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000545421 SCV000898745 uncertain significance Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2018-10-24 criteria provided, single submitter clinical testing IFIH1 NM_022168.3 exon 8 c.1641+1G>C: This variant has not been reported in the literature in association with traditional Mendelian disease, but has been reported as heterozygous in 3 healthy children who were hospitalized due to viral infection (Asgari 2017 PMID:28716935). This variant is present in 1% (1362/125804) of European alleles, including 7 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-163136505-C-G). This variant is present in ClinVar (Variation ID:261563) with at least 2 labs classifying this variant as Benign. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. However, there is limited evidence for this gene and to support loss of function (LOF) as a known disease mechanism. In vitro functional studies suggest that this variant will impact the protein by causing an in-frame loss of 39 amino acids and the skipping of exon 8; thus potentially disrupting signaling function, enzymatic activity and protein stability (Asgari 2017 PMID:28716935). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000545421 SCV000655023 benign Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7 2018-01-03 criteria provided, single submitter clinical testing
PreventionGenetics RCV000245122 SCV000314018 benign not specified criteria provided, single submitter clinical testing

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