Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569055 | SCV000675331 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-05 | criteria provided, single submitter | clinical testing | The p.S176G variant (also known as c.526A>G), located in coding exon 3 of the TMEM127 gene, results from an A to G substitution at nucleotide position 526. The serine at codon 176 is replaced by glycine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000806090 | SCV000946071 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 176 of the TMEM127 protein (p.Ser176Gly). 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: 486548). 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. |
St. |
RCV002291674 | SCV002584550 | uncertain significance | Pheochromocytoma | 2022-07-03 | criteria provided, single submitter | clinical testing | The TMEM127 c.526A>G (p.Ser176Gly) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in the literature in individuals with paraganglioma or pheochromocytoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Baylor Genetics | RCV002291674 | SCV004206169 | uncertain significance | Pheochromocytoma | 2023-08-12 | criteria provided, single submitter | clinical testing |