Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Advanced Laboratory Medicine, |
RCV000852684 | SCV000995393 | likely benign | Hypertrophic cardiomyopathy | 2017-12-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004029272 | SCV002705144 | uncertain significance | not specified | 2023-07-10 | criteria provided, single submitter | clinical testing | The c.1549G>A (p.A517T) alteration is located in exon 4 (coding exon 4) of the TMPO gene. This alteration results from a G to A substitution at nucleotide position 1549, causing the alanine (A) at amino acid position 517 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV002538868 | SCV003255987 | uncertain significance | Loeys-Dietz syndrome 2 | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 517 of the TMPO protein (p.Ala517Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 691729). 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. |