ClinVar Miner

Submissions for variant NM_024753.5(TTC21B):c.264_267dupTAGA

dbSNP: rs748514860
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Juno Genomics, Hangzhou Juno Genomics, Inc RCV005867156 SCV007495825 pathogenic Nephronophthisis 12 criteria provided, single submitter clinical testing Absent from controls (or at extremely low frequency if recessive) in Genome Aggregation Database, Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.;Null variant in a gene where loss of function (LOF) is a known mechanism of disease.;For recessive disorders, detected in trans with a pathogenic variant.;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology.
3billion RCV005867156 SCV006585161 pathogenic Nephronophthisis 12 2024-11-27 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: <0.001%). Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV001179137 /PMID: 23559409). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV003771653 SCV004569694 pathogenic Jeune thoracic dystrophy; Nephronophthisis 2023-12-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu90*) in the TTC21B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC21B are known to be pathogenic (PMID: 18327258, 21068128, 21258341, 23559409, 24876116, 25492405, 27491411, 29068549). This variant is present in population databases (rs748514860, gnomAD 0.08%). This premature translational stop signal has been observed in individual(s) with TTC21B-related conditions (PMID: 23559409, 25492405, 36263627). ClinVar contains an entry for this variant (Variation ID: 1179137). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001536012 SCV001752692 pathogenic Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 2021-06-30 criteria provided, single submitter clinical testing
Department of Pediatrics, National Cheng-Kung University Hospital RCV003339667 SCV004046853 uncertain significance Bardet-Biedl syndrome 2 no assertion criteria provided clinical testing

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