ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.3032T>C (p.Met1011Thr)

gnomAD frequency: 0.00001  dbSNP: rs777427926
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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 RCV001996784 SCV002226587 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-03-09 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1011 of the TTC21B protein (p.Met1011Thr). This variant is present in population databases (rs777427926, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. 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 tolerated. 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 RCV005016927 SCV005651227 uncertain significance Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2024-04-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538668 SCV004713086 uncertain significance TTC21B-related disorder 2024-01-29 no assertion criteria provided clinical testing The TTC21B c.3032T>C variant is predicted to result in the amino acid substitution p.Met1011Thr. This variant has been reported in the singly heterozygous status in an individual undergoing Joubert syndrome testing, but was stated to be unlikely the main explanation for disease due to previous reports of this gene's association with autosomal recessive inheritance (Srour et al. 2012. PubMed ID: 22425360). This variant is reported in 0.0027% 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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