Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000539377 | SCV000646403 | uncertain significance | Loeys-Dietz syndrome 2 | 2023-09-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TMPO-related conditions. 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. 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 TMPO protein function. ClinVar contains an entry for this variant (Variation ID: 469134). This variant is present in population databases (rs376074187, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 300 of the TMPO protein (p.His300Tyr). |
| Ambry Genetics | RCV004024076 | SCV002684030 | uncertain significance | not specified | 2023-09-06 | criteria provided, single submitter | clinical testing | The p.H300Y variant (also known as c.898C>T), located in coding exon 4 of the TMPO gene, results from a C to T substitution at nucleotide position 898. The histidine at codon 300 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |