ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.407C>T (p.Thr136Met)

gnomAD frequency: 0.00003  dbSNP: rs759138897
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000692850 SCV000820695 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 136 of the TMEM127 protein (p.Thr136Met). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 571648). 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. 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 RCV001021821 SCV001183486 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-30 criteria provided, single submitter clinical testing The p.T136M variant (also known as c.407C>T), located in coding exon 2 of the TMEM127 gene, results from a C to T substitution at nucleotide position 407. The threonine at codon 136 is replaced by methionine, 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.
GeneDx RCV004820092 SCV005440906 uncertain significance not provided 2024-06-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21156949)
Fulgent Genetics, Fulgent Genetics RCV005027859 SCV005663311 uncertain significance Pheochromocytoma 2024-04-18 criteria provided, single submitter clinical testing

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