ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.143G>A (p.Gly48Glu) (rs267606632)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000144434 SCV000831581 likely pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-06-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 48 of the ACVRL1 protein (p.Gly48Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 21158752, 17786384, 24603890). ClinVar contains an entry for this variant (Variation ID: 156350). 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 observation of one or more missense substitutions at this codon (p.Gly48Glu and p.Gly48Arg) in affected individuals suggests that this may be a clinically significant residue (PMID: 15521985, 21158752, 17786384, 24603890, 15024723). 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.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000144434 SCV000189489 not provided Hereditary hemorrhagic telangiectasia type 2 no assertion provided not provided

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