ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.3182A>G (p.Tyr1061Cys)

gnomAD frequency: 0.00004  dbSNP: rs200280772
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519482 SCV000621649 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TTC21B gene. The Y1061C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The Y1061C 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001853689 SCV002126239 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1061 of the TTC21B protein (p.Tyr1061Cys). This variant is present in population databases (rs200280772, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. ClinVar contains an entry for this variant (Variation ID: 452809). 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 TTC21B 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.
Ambry Genetics RCV004965535 SCV005523481 uncertain significance Inborn genetic diseases 2024-11-22 criteria provided, single submitter clinical testing The c.3182A>G (p.Y1061C) alteration is located in exon 24 (coding exon 24) of the TTC21B gene. This alteration results from a A to G substitution at nucleotide position 3182, causing the tyrosine (Y) at amino acid position 1061 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005018896 SCV005651218 uncertain significance Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2024-01-20 criteria provided, single submitter clinical testing

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