ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.179T>A (p.Phe60Tyr)

gnomAD frequency: 0.00005  dbSNP: rs371571631
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002025355 SCV002277123 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 60 of the TTC21B protein (p.Phe60Tyr). This variant is present in population databases (rs371571631, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Meckel-Gruber syndrome (PMID: 21258341). ClinVar contains an entry for this variant (Variation ID: 1483130). 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. Experimental studies have shown that this missense change affects TTC21B function (PMID: 21258341). 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.
GeneDx RCV004591682 SCV005080171 uncertain significance not provided 2024-06-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21258341, 32184807)
PreventionGenetics, part of Exact Sciences RCV004734381 SCV005351390 uncertain significance TTC21B-related disorder 2024-09-06 no assertion criteria provided clinical testing The TTC21B c.179T>A variant is predicted to result in the amino acid substitution p.Phe60Tyr. This variant was reported in one individual from a cohort of ciliopathy patients and was listed as a hypomorph allele based on zebrafish studies (Table S2, Davis et al. 2011. PubMed ID: 21258341). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) 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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