Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001243793 | SCV001416976 | uncertain significance | Loeys-Dietz syndrome 2 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 415 of the TMPO protein (p.Ser415Ala). This variant is present in population databases (rs200367787, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. ClinVar contains an entry for this variant (Variation ID: 968613). 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 with a negative predictive value of 80%. 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 | RCV004034762 | SCV002670332 | uncertain significance | not specified | 2021-09-16 | criteria provided, single submitter | clinical testing | The c.1243T>G (p.S415A) alteration is located in exon 4 (coding exon 4) of the TMPO gene. This alteration results from a T to G substitution at nucleotide position 1243, causing the serine (S) at amino acid position 415 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Dept of Medical Biology, |
RCV003318398 | SCV004022085 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PM2 |
Ce |
RCV003393910 | SCV004129738 | likely benign | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | TMPO: BP4 |