ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1046T>C (p.Leu349Pro) (rs765895870)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819566 SCV000960233 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 349 of the ACVRL1 protein (p.Leu349Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs765895870, ExAC 0.002%). This variant has been observed to segregate with hereditary hemorrhagic telangiectasia (HHT) in a family and in individuals affected with HHT (PMID: 24001356, 20414677, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV001507810 SCV001713604 likely pathogenic not provided 2020-07-29 criteria provided, single submitter clinical testing PP1_Strong, PM1, PM2, PP3

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