Submissions for variant NM_182919.4(TICAM1):c.1702G>A (p.Ala568Thr)

gnomAD frequency: 0.00269  dbSNP: rs143679494

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000543404	SCV000652805	likely benign	Herpes simplex encephalitis, susceptibility to, 4	2025-02-03	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000543404	SCV001468471	uncertain significance	Herpes simplex encephalitis, susceptibility to, 4	2021-03-30	criteria provided, single submitter	clinical testing	TICAM1 NM_182919.3 exon 2 p.Ala568Thr (c.1702G>A): This variant has been reported in the literature in at least 1 individual with a history of Herpes simplex encephalitis (HSE) (Mork 2015 PMID:26513235, Andersen 2019 PMID:29217828). This variant is present in 0.3% (503/128998) of European alleles, including 1 homozygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-4816688-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:473292). This variant amino acid Threonine (Thr) is present in 5 species (Pika, Elephant, Saker falcon, Peregrine falcon, Atlantic cod) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In vitro functional studies suggest that this variant will impact the protein (Andersen 2019 PMID:29217828). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001529334	SCV003918037	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	TICAM1: BP4, BS2
OMIM	RCV000543404	SCV000693866	risk factor	Herpes simplex encephalitis, susceptibility to, 4	2018-03-15	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529334	SCV001742602	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529334	SCV001932903	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004757247	SCV005345048	likely benign	TICAM1-related disorder	2024-08-13	no assertion criteria provided	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).