ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.568G>A (p.Ala190Thr)

dbSNP: rs373781978
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001211504 SCV001383045 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 190 of the TMEM127 protein (p.Ala190Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndrome (PMID: 28384794, 33051659). ClinVar contains an entry for this variant (Variation ID: 941668). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TMEM127 function (PMID: 32575117). 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 RCV002348694 SCV002648215 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-27 criteria provided, single submitter clinical testing The p.A190T variant (also known as c.568G>A), located in coding exon 3 of the TMEM127 gene, results from a G to A substitution at nucleotide position 568. The alanine at codon 190 is replaced by threonine, 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.
Baylor Genetics RCV003462709 SCV004206179 uncertain significance Pheochromocytoma 2023-05-26 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.