ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.2941C>T (p.Arg981Cys)

gnomAD frequency: 0.00001  dbSNP: rs749278599
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001765256 SCV001989773 uncertain significance not provided 2019-05-13 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002032838 SCV002278917 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 981 of the TTC21B protein (p.Arg981Cys). This variant is present in population databases (rs749278599, gnomAD 0.01%). 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: 1305887). 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.
Fulgent Genetics, Fulgent Genetics RCV002496090 SCV002781661 uncertain significance Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2023-12-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV005286500 SCV005960775 uncertain significance Inborn genetic diseases 2025-01-29 criteria provided, single submitter clinical testing The c.2941C>T (p.R981C) alteration is located in exon 22 (coding exon 22) of the TTC21B gene. This alteration results from a C to T substitution at nucleotide position 2941, causing the arginine (R) at amino acid position 981 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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