Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071122 | SCV001236410 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-04-28 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 864030). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 38 of the TMEM127 protein (p.Ala38Ser). |
| St. |
RCV001071122 | SCV001737491 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2021-05-13 | criteria provided, single submitter | clinical testing | The TMEM127 c.112G>T (p.Ala38Ser) missense change has a maximum subpopulation frequency of 0.0067% in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/2-96931008-C-T?dataset=gnomad_r2_1). In silico tools are not in agreement about the effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in the literature in individuals with paraganglioma or pheochromocytoma. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting. |
| Ambry Genetics | RCV002320353 | SCV002607633 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.A38S variant (also known as c.112G>T), located in coding exon 1 of the TMEM127 gene, results from a G to T substitution at nucleotide position 112. The alanine at codon 38 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003462618 | SCV004206168 | uncertain significance | Pheochromocytoma | 2023-08-13 | criteria provided, single submitter | clinical testing |