ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.119C>T (p.Ser40Phe)

dbSNP: rs1684392721
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001231689 SCV001404220 uncertain significance Hereditary pheochromocytoma-paraganglioma 2022-11-14 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 958508). This missense change has been observed in individual(s) with pheochromocytoma (PMID: 28458909). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 40 of the TMEM127 protein (p.Ser40Phe). 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 RCV003373064 SCV004096451 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing The p.S40F variant (also known as c.119C>T), located in coding exon 1 of the TMEM127 gene, results from a C to T substitution at nucleotide position 119. The serine at codon 40 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been observed in at least two individuals with a pheochromocytoma or paraganglioma (Yonamine M et al. Cancers (Basel). 2021 Aug;13; Ambry internal data). This alteration was also detected in an individual with a pheochromocytoma whose father was also diagnosed with a pheochromocytoma (Saitoh K et al. Endocrinol Diabetes Metab Case Rep. 2017 Apr;2017:). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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