Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001926430 | SCV002207347 | uncertain significance | Loeys-Dietz syndrome 2 | 2021-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 314 of the TMPO protein (p.Ile314Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV004044185 | SCV002687162 | uncertain significance | not specified | 2022-10-21 | criteria provided, single submitter | clinical testing | The p.I314M variant (also known as c.942T>G), located in coding exon 4 of the TMPO gene, results from a T to G substitution at nucleotide position 942. The isoleucine at codon 314 is replaced by methionine, an amino acid with highly 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. |