Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001304507 | SCV001493792 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 235 of the TTC21B protein (p.Ala235Pro). This variant is present in population databases (rs150742619, gnomAD 0.02%). This missense change has been observed in individual(s) with asphyxiating thoracic dystrophy (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446647). 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. |
Dan Cohn Lab, |
RCV000516004 | SCV000612061 | likely pathogenic | Jeune thoracic dystrophy | 2017-06-01 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV000516004 | SCV001479413 | likely pathogenic | Jeune thoracic dystrophy | no assertion criteria provided | research |