ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1160T>C (p.Leu387Pro)

dbSNP: rs1564453623
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel, ClinGen RCV003989116 SCV004805870 uncertain significance Telangiectasia, hereditary hemorrhagic, type 1 2024-03-15 reviewed by expert panel curation The NM_001114753.3: c.1160T>C variant in ENG is a missense variant predicted to cause substitution of leucine by proline at amino acid 387 (p.Leu387Pro). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.78, which is above the threshold of greater than or equal to 0.644, evidence that correlates with impact to ENG function (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: PM2_Supporting, PP3 (specification version 1.0.0; 1/4/2024).
Invitae RCV002233115 SCV000812637 likely pathogenic Hereditary hemorrhagic telangiectasia 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 387 of the ENG protein (p.Leu387Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 565574). 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 with a positive predictive value of 95%. 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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