Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001977883 | SCV002262362 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 15 of the TMEM127 protein (p.Arg15Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. ClinVar contains an entry for this variant (Variation ID: 1476296). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Baylor Genetics | RCV003464345 | SCV004206167 | uncertain significance | Pheochromocytoma | 2023-08-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004946964 | SCV005517134 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-01 | criteria provided, single submitter | clinical testing | The p.R15L variant (also known as c.44G>T), located in coding exon 1 of the TMEM127 gene, results from a G to T substitution at nucleotide position 44. The arginine at codon 15 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999582 | SCV005626229 | uncertain significance | not provided | 2024-02-16 | criteria provided, single submitter | clinical testing | The TMEM127 c.44G>T (p.Arg15Leu) variant has not been reported in individuals with TMEM127-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org), however the frequency may be unreliable due to suboptimal data quality. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |