ClinVar Miner

Submissions for variant NM_003265.3(TLR3):c.554C>T (p.Ala185Val)

gnomAD frequency: 0.00048  dbSNP: rs35140061
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691916 SCV000819715 uncertain significance Herpes simplex encephalitis, susceptibility to, 1 2023-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 185 of the TLR3 protein (p.Ala185Val). This variant is present in population databases (rs35140061, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. 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: 570922). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224374 SCV003920564 uncertain significance Susceptibility to HIV infection; Immunodeficiency 83, susceptibility to viral infections 2022-06-03 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.1% (62/41402) (https://gnomad.broadinstitute.org/variant/4-186078952-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:570922). This variant amino acid Valine (Val) is present in several species including multiple mammals 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 summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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