Submissions for variant NM_022168.4(IFIH1):c.1557_1558del (p.Lys519fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003797457	SCV004586440	likely benign	Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7	2023-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767468	SCV005380373	uncertain significance	not specified	2024-08-22	criteria provided, single submitter	clinical testing	Variant summary: IFIH1 c.1557_1558delAA (p.Lys519AsnfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however current evidence is not sufficient to establish loss of function as a mechanism for disease. The variant was absent in 249670 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1557_1558delAA in individuals affected with Aicardi-Goutieres Syndrome 7 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2940099). Based on the evidence outlined above, the variant was classified as uncertain significance.