ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.7C>T (p.Arg3Cys) (rs139334561)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001034662 SCV000546111 uncertain significance Hereditary hemorrhagic telangiectasia 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 3 of the ENG protein (p.Arg3Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs139334561, ExAC 0.09%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with hereditary hemorrhagic telangiectasia type 1, however in this individual a second variant considered a non-functional allele was also observed in a different gene (PMID: 15312062). ClinVar contains an entry for this variant (Variation ID: 374952). Experimental studies have shown that ENG protein with this missense change is able to correctly localize to the cell surface and respond to BMP9 signaling in vitro (PMID: 25312062). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488039 SCV000575593 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000415646 SCV001332251 likely benign Hereditary hemorrhagic telangiectasia type 1 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000415646 SCV001439459 likely benign Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research BS1 +BP2
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000415646 SCV000493740 uncertain significance Hereditary hemorrhagic telangiectasia type 1 2016-01-27 no assertion criteria provided clinical testing

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