Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001239717 | SCV001412611 | uncertain significance | Loeys-Dietz syndrome 2 | 2019-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with cysteine at codon 654 of the TMPO protein (p.Trp654Cys). The tryptophan residue is weakly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TMPO-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV004034625 | SCV005020599 | uncertain significance | not specified | 2023-12-25 | criteria provided, single submitter | clinical testing | The p.W654C variant (also known as c.1962G>C), located in coding exon 4 of the TMPO gene, results from a G to C substitution at nucleotide position 1962. The tryptophan at codon 654 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |