ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.806T>G (p.Met269Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206664 SCV001377984 pathogenic Hereditary hemorrhagic telangiectasia 2020-09-17 criteria provided, single submitter clinical testing This sequence change replaces methionine with arginine at codon 269 of the ENG protein (p.Met269Arg). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hereditary hemorrhagic telangiectasia (PMID: 20414677, Invitae). ClinVar contains an entry for this variant (Variation ID: 937612). 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: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Met269 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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