Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000698079 | SCV000826721 | uncertain significance | Loeys-Dietz syndrome 2 | 2018-02-13 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with TMPO-related disease. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 643 of the TMPO protein (p.Met643Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. |
Ambry Genetics | RCV004026428 | SCV002717465 | uncertain significance | not specified | 2022-02-04 | criteria provided, single submitter | clinical testing | The p.M643V variant (also known as c.1927A>G), located in coding exon 4 of the TMPO gene, results from an A to G substitution at nucleotide position 1927. The methionine at codon 643 is replaced by valine, an amino acid with highly similar 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. |