ClinVar Miner

Submissions for variant NM_144596.4(TTC8):c.1051C>T (p.Arg351Trp)

gnomAD frequency: 0.00006  dbSNP: rs755412340
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479252 SCV000572709 uncertain significance not provided 2017-02-03 criteria provided, single submitter clinical testing The R341W variant in the TTC8 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R341W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R341W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R341W as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000765184 SCV000896419 uncertain significance Retinitis pigmentosa 51; Bardet-Biedl syndrome 8 2024-05-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001352193 SCV001546730 uncertain significance Bardet-Biedl syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 341 of the TTC8 protein (p.Arg341Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs755412340, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with TTC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 423070). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
New York Genome Center RCV003335373 SCV004046578 uncertain significance Bardet-Biedl syndrome 8 2022-10-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004722823 SCV005338885 uncertain significance TTC8-related disorder 2024-09-17 no assertion criteria provided clinical testing The TTC8 c.1051C>T variant is predicted to result in the amino acid substitution p.Arg351Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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