Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001979851 | SCV002221251 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 399 of the TTC21B protein (p.Tyr399His). This variant is present in population databases (rs187985767, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TTC21B protein function. 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 | RCV004043824 | SCV004972677 | uncertain significance | Inborn genetic diseases | 2024-01-03 | criteria provided, single submitter | clinical testing | The c.1195T>C (p.Y399H) alteration is located in exon 11 (coding exon 11) of the TTC21B gene. This alteration results from a T to C substitution at nucleotide position 1195, causing the tyrosine (Y) at amino acid position 399 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005016928 | SCV005651287 | uncertain significance | Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 | 2024-06-18 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004734365 | SCV005352369 | uncertain significance | TTC21B-related disorder | 2024-08-19 | no assertion criteria provided | clinical testing | The TTC21B c.1195T>C variant is predicted to result in the amino acid substitution p.Tyr399His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-166785836-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |