ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.620G>T (p.Cys207Phe)

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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 RCV001287270 SCV001473944 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 2020-03-02 criteria provided, single submitter clinical testing The ENG c.620G>T; p.Cys207Phe variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 207 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, two other variants at this codon (p.Cys207Tyr, p.Cys207Arg) have been reported in individuals with HHT (see HHT database link, Mallet 2015). The p.Cys207Arg variant was also shown to co-segregate with disease, and functional analyses of the variant protein showed mislocalization and complete inactivation (Mallet 2015). Based on available information, the p.Cys207Phe variant is considered to be likely pathogenic. REFERENCES Link to ENG HHT database: Mallet C et al. Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function. Hum Mol Genet. 2015 Feb 15;24(4):1142-54.

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