Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002607494 | SCV003510702 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1003 of the TTC21B protein (p.Glu1003Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 2192481). 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 with a negative predictive value of 95%. 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 | RCV004963502 | SCV005523476 | uncertain significance | Inborn genetic diseases | 2024-09-30 | criteria provided, single submitter | clinical testing | The c.3007G>A (p.E1003K) alteration is located in exon 23 (coding exon 23) of the TTC21B gene. This alteration results from a G to A substitution at nucleotide position 3007, causing the glutamic acid (E) at amino acid position 1003 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |