Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Greenwood Genetic Center Diagnostic Laboratories, |
RCV001804204 | SCV002051746 | uncertain significance | not provided | 2021-02-02 | criteria provided, single submitter | clinical testing | PM3, PM2 |
Labcorp Genetics |
RCV001804204 | SCV003443021 | likely pathogenic | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1331679). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 771 of the TELO2 protein (p.Leu771Ser). This variant is present in population databases (rs201230315, gnomAD 0.02%). This missense change has been observed in individual(s) with You-Hoover-Fong syndrome (PMID: 28944240). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. 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 TELO2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |