Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003265(TLR3):c.1234C>G(p.Leu412Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000855 in 152026 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L412F) has been classified as Likely benign.
Verdict is Uncertain_significance.
GnomAD3 genomes AF: 0.0000855AC: 13AN: 152026Hom.: 0Cov.: 32 GnomAD3 exomes AF: 0.000124AC: 31AN: 250924Hom.: 0 AF XY: 0.000103AC XY: 14AN XY: 135724 GnomAD4 exome AF: 0.000324AC: 473AN: 1461792Hom.: 1 AF XY: 0.000319AC XY: 232AN XY: 727180
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1
|Uncertain significance, criteria provided, single submitter||clinical testing||Invitae||Oct 23, 2022||This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 412 of the TLR3 protein (p.Leu412Val). This variant is present in population databases (rs3775291, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TLR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 656784). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -|
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