ClinVar Miner

Submissions for variant NM_015631.6(TCTN3):c.1070A>G (p.Gln357Arg)

gnomAD frequency: 0.00006  dbSNP: rs151123934
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001576269 SCV001803423 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing Reported heterozygous in a patient with a clinical diagnosis of Joubert syndrome who also was heterozygous for a truncating variant in the KIAA0586 gene (Bachmann-Gagescu et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26096313)
Labcorp Genetics (formerly Invitae), Labcorp RCV001866066 SCV002271420 uncertain significance Orofacial-digital syndrome IV; Joubert syndrome 18 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 357 of the TCTN3 protein (p.Gln357Arg). This variant is present in population databases (rs151123934, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TCTN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1208077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TCTN3 protein function with a negative predictive value of 80%. 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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