ClinVar Miner

Submissions for variant NM_001193304.3(TMEM127):c.217G>C (p.Gly73Arg) (rs121908820)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542037 SCV000637914 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2020-08-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 73 of the TMEM127 protein (p.Gly73Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs121908820, ExAC 0.01%). This variant has been reported in an individual affected with a pheochromocytoma (PMID: 21156949). ClinVar contains an entry for this variant (Variation ID: 126965). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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 RCV001014707 SCV001175451 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing The p.G73R variant (also known as c.217G>C), located in coding exon 1 of the TMEM127 gene, results from a G to C substitution at nucleotide position 217. The glycine at codon 73 is replaced by arginine, an amino acid with dissimilar properties. This variant has been detected in an Italian male with an apparently sporadic adrenal paraganglioma at age 44y (Yao L et al, JAMA 2010 Dec; 304(23):2611-9). 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.
Familial Cancer Clinic,Veneto Institute of Oncology RCV000114823 SCV000148718 likely pathogenic - adrenal pheochromocytoma Pheochromocytoma no assertion criteria provided not provided Converted during submission to Likely pathogenic.
CSER _CC_NCGL, University of Washington RCV000114823 SCV000190640 likely benign Pheochromocytoma 2014-06-01 no assertion criteria provided research

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