ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.806T>A (p.Met269Lys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001381129 SCV001579382 pathogenic Hereditary hemorrhagic telangiectasia 2020-09-15 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 269 of the ENG protein (p.Met269Lys). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENG protein function. This variant disrupts the p.Met269 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20414677, 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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