ClinVar Miner

Submissions for variant NM_182919.3(TICAM1):c.557C>T (p.Ser186Leu) (rs146550489)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000030824 SCV000652809 uncertain significance Herpes simplex encephalitis, susceptibility to, 4 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 186 of the TICAM1 protein (p.Ser186Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs146550489, ExAC 0.1%). This variant has been reported as a heterozygous variant in an individual affected with herpes simplex encephalitis (PMID: 22105173). Two other individuals in this family also carried this variant and were unaffected, although both had HSV-1 specific serum antibodies. The TICAM1 gene is also known as TRIF in the literature. ClinVar contains an entry for this variant (Variation ID: 37266). Experimental studies have shown that while this missense change appears functional in a transiently transfected cell line, studies of this variant performed in patient fibroblasts or retrovirally transduced TICAM1 deficient fibroblasts demonstrate significantly impaired TLR3 responses, suggesting this change may be a hypomorphic variant (PMID: 22105173). 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.
OMIM RCV000030824 SCV000053499 risk factor Herpes simplex encephalitis, susceptibility to, 4 2011-12-01 no assertion criteria provided literature only

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