Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003062954 | SCV003450781 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2023-08-30 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 2144394). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. This variant is present in population databases (rs768255232, gnomAD 0.03%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 864 of the TTC21B protein (p.Val864Ile). |
| Ambry Genetics | RCV004070336 | SCV004972687 | uncertain significance | Inborn genetic diseases | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.2590G>A (p.V864I) alteration is located in exon 20 (coding exon 20) of the TTC21B gene. This alteration results from a G to A substitution at nucleotide position 2590, causing the valine (V) at amino acid position 864 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005019614 | SCV005651242 | uncertain significance | Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 | 2024-05-14 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004736256 | SCV005350134 | uncertain significance | TTC21B-related disorder | 2024-07-25 | no assertion criteria provided | clinical testing | The TTC21B c.2590G>A variant is predicted to result in the amino acid substitution p.Val864Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% 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. |