ClinVar Miner

Submissions for variant NM_001193304.3(TMEM127):c.117_120del (p.Ile41fs) (rs121908816)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000449515 SCV000537698 pathogenic Pheochromocytoma 2016-07-12 criteria provided, single submitter clinical testing
GeneDx RCV000485576 SCV000567003 pathogenic not provided 2017-07-10 criteria provided, single submitter clinical testing This deletion of four nucleotides in TMEM127 is denoted c.117_120delGTCT at the cDNA level and p.Ile41ArgfsX39 (I41RfsX39) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CCCT[delGTCT]ATCA. The deletion causes a frameshift which changes an Isoleucine to an Arginine at codon 41, and creates a premature stop codon at position 39 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TMEM127 c.117_120delGTCT, also denoted c.116_119delTGTC and c.115_118delCTGT using alternate nomenclature, has been reported in individuals with early-onset and bilateral pheochromocytomas (Yao 2010, Takeichi 2012, Curr?s-Freixes 2015). We consider this variant to be pathogenic.
Invitae RCV000556401 SCV000637904 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2020-06-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile41Argfs*39) in the TMEM127 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with adrenal pheochromocytoma (PMID: 21156949, 22541004). It is also known as c.116_119delTGTC in the literature. ClinVar contains an entry for this variant (Variation ID: 126962). Loss-of-function variants in TMEM127 are known to be pathogenic (PMID: 21156949). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000574362 SCV000675298 pathogenic Hereditary cancer-predisposing syndrome 2017-05-12 criteria provided, single submitter clinical testing The c.117_120delGTCT pathogenic mutation, located in coding exon 1 of the TMEM127 gene, results from a deletion of 4 nucleotides at nucleotide positions 117 to 120, causing a translational frameshift with a predicted alternate stop codon (p.I41Rfs*39). This mutation (designated as c.116_119delTGTC) has been identified in individuals diagnosed with paragangliomas and pheochromocytomas (Takeichi N et al. Clin. Endocrinol. (Oxf), 2012 Nov;77:707-14; Yao L et al. JAMA, 2010 Dec;304:2611-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Familial Cancer Clinic,Veneto Institute of Oncology RCV000449515 SCV000148714 likely pathogenic - adrenal pheochromocytoma Pheochromocytoma no assertion criteria provided not provided Converted during submission to Likely pathogenic.
GenomeConnect - Invitae Patient Insights Network RCV000449515 SCV001749822 not provided Pheochromocytoma no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 10-11-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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