Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000457015 | SCV000543178 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2024-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 207 of the TMEM127 protein (p.Ala207Val). This variant is present in population databases (rs751044006, gnomAD 0.003%). 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: 405198). 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 disruptive. 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 | RCV002356647 | SCV002655075 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | The p.A207V variant (also known as c.620C>T), located in coding exon 3 of the TMEM127 gene, results from a C to T substitution at nucleotide position 620. The alanine at codon 207 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV005027502 | SCV005663309 | uncertain significance | Pheochromocytoma | 2024-03-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003899903 | SCV004715574 | uncertain significance | TMEM127-related disorder | 2024-02-08 | no assertion criteria provided | clinical testing | The TMEM127 c.620C>T variant is predicted to result in the amino acid substitution p.Ala207Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant is interpreted as uncertain by multiple laboratories (https://www.ncbi.nlm.nih.gov/clinvar/variation/405198/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |