Submissions for variant NM_003265.3(TLR3):c.2269_2270insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAGAACAGTTTGAATATG (p.Ala757fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003024948	SCV003333052	uncertain significance	Herpes simplex encephalitis, susceptibility to, 1	2022-03-31	criteria provided, single submitter	clinical testing	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. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to disrupt protein function (PMID: 19763152, 20307669, 22406018). However the effect of this particular variant is unknown. This variant has not been reported in the literature in individuals affected with TLR3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the TLR3 gene (c.2269_2270ins?), causing a frameshift at codon 757 (p.Ala757fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product.