Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001066831 | SCV001231852 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2019-01-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TMEM127 gene (p.Gln206*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acids of the TMEM127 protein. This variant has not been reported in the literature in individuals with TMEM127-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. |
KCCC/NGS Laboratory, |
RCV003315446 | SCV004015253 | uncertain significance | Pheochromocytoma | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the TMEM127 gene (p.Gln206*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acids of the TMEM127 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TMEM127-related conditions. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Pathogenic computational verdict based on 5 pathogenic predictions from BayesDel_addAF, DANN, EIGEN, FATHMM-MKL and MutationTaster were all deleterious with no benign predictions. Therefore, it has been classified as a Variant of Uncertain Significance. |