Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001237759 | SCV001410533 | uncertain significance | Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 239 of the TRNT1 protein (p.Trp239Ser). This variant is present in population databases (rs753464075, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TRNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 963696). 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 expected to disrupt TRNT1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |