Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003061658 | SCV003461929 | uncertain significance | Loeys-Dietz syndrome 2 | 2023-06-16 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2152399). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 77 of the TMPO protein (p.Leu77Phe). |
| Ambry Genetics | RCV004071720 | SCV005020357 | uncertain significance | not specified | 2024-02-16 | criteria provided, single submitter | clinical testing | The p.L77F variant (also known as c.229C>T), located in coding exon 1 of the TMPO gene, results from a C to T substitution at nucleotide position 229. The leucine at codon 77 is replaced by phenylalanine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear. |