ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.902G>A (p.Arg301His)

gnomAD frequency: 0.00002  dbSNP: rs747866883
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002766644 SCV003025422 uncertain significance Jeune thoracic dystrophy; Nephronophthisis 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 301 of the TTC21B protein (p.Arg301His). This variant is present in population databases (rs747866883, gnomAD 0.004%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV003250589 SCV003951206 uncertain significance Inborn genetic diseases 2023-03-28 criteria provided, single submitter clinical testing The c.902G>A (p.R301H) alteration is located in exon 9 (coding exon 9) of the TTC21B gene. This alteration results from a G to A substitution at nucleotide position 902, causing the arginine (R) at amino acid position 301 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003319531 SCV004023915 uncertain significance not provided 2023-07-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004736208 SCV005349250 uncertain significance TTC21B-related disorder 2024-08-14 no assertion criteria provided clinical testing The TTC21B c.902G>A variant is predicted to result in the amino acid substitution p.Arg301His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0036% 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.