ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.419G>A (p.Cys140Tyr)

dbSNP: rs121908828
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003517135 SCV004292623 uncertain significance Hereditary pheochromocytoma-paraganglioma 2022-11-25 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Cys140 amino acid residue in TMEM127. Other variant(s) that disrupt this residue have been observed in individuals with TMEM127-related conditions (PMID: 21156949), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects TMEM127 function (PMID: 21156949). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 126971). This missense change has been observed in individuals with clinical features of TMEM127-related condition (PMID: 21156949, 28384794). This variant is present in population databases (rs121908828, gnomAD 0.006%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 140 of the TMEM127 protein (p.Cys140Tyr).
Familial Cancer Clinic, Veneto Institute of Oncology RCV000114831 SCV000148726 likely pathogenic - adrenal bilateral pheochromocy Pheochromocytoma no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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