ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.23T>C (p.Leu8Pro)

dbSNP: rs1564466414
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002232818 SCV000812361 pathogenic Hereditary hemorrhagic telangiectasia 2025-01-19 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 8 of the ENG protein (p.Leu8Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 15024723, 19767588). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 565357). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ENG protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002442411 SCV002732565 pathogenic Cardiovascular phenotype 2022-11-22 criteria provided, single submitter clinical testing The p.L8P pathogenic mutation (also known as c.23T>C), located in coding exon 1 of the ENG gene, results from a T to C substitution at nucleotide position 23. The leucine at codon 8 is replaced by proline, an amino acid with similar properties. This mutation has been reported in multiple individuals with hereditary hemorrhagic telangiectasia (HHT) and has shown strong segregation with disease (Lesca G et al. Hum. Mutat., 2004 Apr;23:289-99; McDonald J et al. J Mol Diagn, 2009 Nov;11:569-75). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Mayo Clinic Laboratories, Mayo Clinic RCV004792371 SCV005413918 likely pathogenic not provided 2024-07-25 criteria provided, single submitter clinical testing BP4_strong, PP1_strong, PP4, PM2, PS4_moderate

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