ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1220A>G (p.Glu407Gly) (rs1565595121)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691776 SCV000819567 likely pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 407 of the ACVRL1 protein (p.Glu407Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary hemorrhagic telangiectasia in a family (PMID: 18495117). 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. The p.Glu407 amino acid residue in ACVRL1 has been determined to be clinically significant (PMID: 12843319, 15712270, 23722869). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.

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