ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.1231C>G (p.Arg411Gly)

dbSNP: rs185089786
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522845 SCV000617784 uncertain significance not provided 2022-10-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21258341)
Labcorp Genetics (formerly Invitae), Labcorp RCV001240289 SCV001413220 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 411 of the TTC21B protein (p.Arg411Gly). This variant is present in population databases (rs185089786, gnomAD 0.02%). 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: 449539). 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.
Fulgent Genetics, Fulgent Genetics RCV002490903 SCV002790551 uncertain significance Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2022-02-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004735591 SCV005355652 uncertain significance TTC21B-related disorder 2024-08-06 no assertion criteria provided clinical testing The TTC21B c.1231C>G variant is predicted to result in the amino acid substitution p.Arg411Gly. This variant has been reported in an individual with Bardet-Biedl syndrome who also had a homozygous frameshift variant in BBS7 (Davis et al. 2011. PubMed ID: 21258341). Functional analysis of this variant indicated this variant may be a hypomorphic allele (Davis et al. 2011. PubMed ID: 21258341). At this time, the clinical significance of this variant is uncertain.

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