Submissions for variant NM_017849.4(TMEM127):c.565C>T (p.Leu189=)

gnomAD frequency: 0.00022  dbSNP: rs146965678

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163493	SCV000214050	likely benign	Hereditary cancer-predisposing syndrome	2014-11-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234199	SCV000290384	benign	Hereditary pheochromocytoma-paraganglioma	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000404591	SCV000432540	benign	Pheochromocytoma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000439997	SCV000518964	likely benign	not specified	2016-09-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000439997	SCV002070970	likely benign	not specified	2020-03-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163493	SCV002527261	likely benign	Hereditary cancer-predisposing syndrome	2021-05-18	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001723732	SCV002563582	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	TMEM127: BP4, BS1, BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000404591	SCV004015621	benign	Pheochromocytoma	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001723732	SCV005259871	likely benign	not provided		criteria provided, single submitter	not provided
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723732	SCV001951456	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723732	SCV001971128	likely benign	not provided		no assertion criteria provided	clinical testing