ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1089T>G (p.Cys363Trp) (rs777177134)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757222 SCV000885368 uncertain significance not provided 2018-05-09 criteria provided, single submitter clinical testing The ENG c.1089T>G; p.Cys363Trp variant, to our knowledge, is not reported in the medical literature or gene specific databases. However, other variants at this codon (p.Cys363Ser, p.Cys363Tyr) are reported in the literature in individuals with HHT (Bossler 2006, Gedge 2007, Nishida 2012, Paquet 2001), and the p.Cys363Tyr variant improperly localizes to the endoplasmic reticulum (Ali 2011). The p.Cys363Trp variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 363 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information regarding p.Cys363Trp, its clinical significance is uncertain at this time. References: Ali BR et al. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia. PLoS One. 2011;6(10):e26206. Bossler AD et al. Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat. 2006 Jul;27(7):667-75. Gedge F et al. Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations. J Mol Diagn. 2007 Apr;9(2):258-65. Nishida T et al. Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Am J Med Genet A. 2012 Nov;158A(11):2829-34. Paquet ME et al. Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum Mol Genet. 2001 Jun 15;10(13):1347-57.

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