Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001320334 | SCV001511116 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 780 of the TTC21B protein (p.Glu780Val). This variant is present in population databases (rs371940683, gnomAD 0.03%). 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: 1020713). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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, |
RCV002476499 | SCV002781487 | uncertain significance | Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 | 2024-03-08 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV003738040 | SCV004564212 | uncertain significance | not provided | 2023-10-09 | criteria provided, single submitter | clinical testing | The TTC21B c.2339A>T; p.Glu780Val variant (rs371940683), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1020713). This variant is observed in thirteen individuals in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamic acid at codon 780 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.751). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time References: None Found |
| Breakthrough Genomics, |
RCV003738040 | SCV005187986 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Prevention |
RCV004734123 | SCV005351278 | uncertain significance | TTC21B-related disorder | 2024-03-26 | no assertion criteria provided | clinical testing | The TTC21B c.2339A>T variant is predicted to result in the amino acid substitution p.Glu780Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |