ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1088G>C (p.Cys363Ser) (rs1588580782)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819037 SCV000959678 likely pathogenic Hereditary hemorrhagic telangiectasia 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 363 of the ENG protein (p.Cys363Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in several individuals with clinical features of hereditary hemorrhagic telangiectasia (HHT) (PMID: 24196379, 17384219, 22991266, 23710379). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys363 amino acid residue in ENG. Other variant(s) that disrupt this residue have been observed in individuals with ENG-related conditions (PMID: 11440987), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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