Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001222875 | SCV001394997 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-06-15 | criteria provided, single submitter | clinical testing | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 951046). 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 variant, c.24_32del, results in the deletion of 3 amino acid(s) of the TMEM127 protein (p.Leu9_Gly11del), but otherwise preserves the integrity of the reading frame. This variant disrupts a region of the TMEM127 protein in which other variant(s) (p.Gly11Cys) have been observed in individuals with TMEM127-related conditions (PMID: 32575117). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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 | RCV002447122 | SCV002732566 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-01 | criteria provided, single submitter | clinical testing | The c.24_32delGCTGCCCGG variant (also known as p.L9_G11del) is located in coding exon 1 of the TMEM127 gene. This variant results from an in-frame GCTGCCCGG deletion at nucleotide positions 24 to 32. This results in the in-frame deletion of leucine, proline, and glycine residues between codons 9 and 11. This amino acid region is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003462760 | SCV004206163 | uncertain significance | Pheochromocytoma | 2023-09-13 | criteria provided, single submitter | clinical testing |