ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.830C>A (p.Thr277Lys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001211474 SCV001383015 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-08-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with lysine at codon 277 of the ACVRL1 protein (p.Thr277Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families with hereditary hemorrhagic telangiectasia or clinical features of this condition (PMID: 25970827, 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. 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.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001211474 SCV001439468 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-01-01 criteria provided, single submitter research PM2+PM1+PP4
Mayo Clinic Laboratories, Mayo Clinic RCV001507807 SCV001713600 pathogenic not provided 2020-02-12 criteria provided, single submitter clinical testing PS4, PM2, PP3, PP1

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