ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.578T>C (p.Leu193Pro)

dbSNP: rs1555152790
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001771919 SCV002001595 uncertain significance not provided 2021-01-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV000660863 SCV002290325 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2024-02-14 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 193 of the ACVRL1 protein (p.Leu193Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant pulmonary hypertension (PMID: 35346192; Invitae). ClinVar contains an entry for this variant (Variation ID: 548119). 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 ACVRL1 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.
Institute of Human Genetics, University of Goettingen RCV000660863 SCV000778829 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-06-28 no assertion criteria provided clinical testing

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