ClinVar Miner

Submissions for variant NM_017849.3(TMEM127):c.280C>T (p.Arg94Trp) (rs121908824)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567548 SCV000675308 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Familial Cancer Clinic,Veneto Institute of Oncology RCV000114826 SCV000148721 likely pathogenic - adrenal pheochromocytoma Pheochromocytoma no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Invitae RCV000229383 SCV000290377 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2018-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 94 of the TMEM127 protein (p.Arg94Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121908824, ExAC 0.006%). This variant has been reported in an individual with pheochromocytoma (PMID: 21156949). ClinVar contains an entry for this variant (Variation ID: 126967). Experimental evidence shows an abnormal subcellular protein localization pattern for this variant compared to wild-type protein (PMID: 21156949). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change that disrupts protein localization in vitro and has an uncertain impact on splicing. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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