Submissions for variant NM_022168.4(IFIH1):c.2524G>A (p.Glu842Lys)

gnomAD frequency: 0.00076  dbSNP: rs79324540

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000542562	SCV000655031	likely benign	Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7	2024-01-23	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000542562	SCV000898743	uncertain significance	Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7	2018-11-19	criteria provided, single submitter	clinical testing	IFIH1 NM_022168.3 exon 13 p.Glu842Lys (c.2524G>A): This variant has not been reported in the literature but is present in 0.07% (101/126416) of European alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-163128828-C-T). This variant is present in ClinVar (Variation ID:474952). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics	RCV002525315	SCV003535479	likely benign	Inborn genetic diseases	2021-10-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224335	SCV003920040	uncertain significance	Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7; Immunodeficiency 95	2021-03-30	criteria provided, single submitter	clinical testing	IFIH1 NM_022168.3 exon 13 p.Glu842Lys (c.2524G>A): This variant has not been reported in the literature but is present in 0.07% (101/126416) of European alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-163128828-C-T). This variant is present in ClinVar (Variation ID:474952). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV003431110	SCV004147077	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	IFIH1: BS2
PreventionGenetics, part of Exact Sciences	RCV003905449	SCV004727573	likely benign	IFIH1-related disorder	2022-01-28	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).