ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.653G>C (p.Arg218Pro) (rs779287554)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458880 SCV000552395 uncertain significance Telangiectasia, hereditary hemorrhagic, type 2 2016-11-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 218 of the ACVRL1 protein (p.Arg218Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ACVRL1-related disease. A different variant (c.653_654delinsCC) giving rise to the same protein effect observed here (p.Arg218Pro) has been reported in two related individuals affected with hereditary haemorrhagic telangiectasia (PMID: 23919827), indicating that this residue may be critical for protein function. 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. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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