Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000528885 | SCV000637907 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2024-11-16 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 45 of the TMEM127 protein (p.Cys45Ser). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 463837). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV001010941 | SCV001171206 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing | The p.C45S variant (also known as c.133T>A), located in coding exon 1 of the TMEM127 gene, results from a T to A substitution at nucleotide position 133. The cysteine at codon 45 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| ARUP Laboratories, |
RCV003114660 | SCV003799243 | uncertain significance | Pheochromocytoma | 2022-03-23 | criteria provided, single submitter | clinical testing | The TMEM127 c.133T>A; p.Cys45Ser variant (rs995979769), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 463837). This variant is found in the non-Finnish European population with an allele frequency of 0.004% (4/13150 alleles) in the Genome Aggregation Database. The cysteine at codon 45 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.59). However, given the lack of clinical and functional data, the significance of the p.Cys45Ser variant is uncertain at this time. |
| Baylor Genetics | RCV003114660 | SCV004203881 | uncertain significance | Pheochromocytoma | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV005000162 | SCV005626220 | uncertain significance | not provided | 2024-09-02 | criteria provided, single submitter | clinical testing | The TMEM127 c.133T>A (p.Cys45Ser) variant has not been reported in individuals with TMEM127-related conditions in the published literature. The frequency of this variant in the general population, 0.000042 (4/94296 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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. |