ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.914C>T (p.Ser305Phe) (rs1555153126)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000808864 SCV000602420 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-09-25 criteria provided, single submitter clinical testing
Invitae RCV000808864 SCV000948991 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2020-06-27 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 305 of the ACVRL1 protein (p.Ser305Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in to segregate in a family affected with hereditary hemorrhagic telangiectasia (Invitae) and has been observed in unrelated individuals affected with this disease (PMID: 17384219, 29171923, Invitae). ClinVar contains an entry for this variant (Variation ID: 439382). 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.Ser305Phe and p.Ser305Pro) in affected individuals suggests that this may be a clinically significant residue (PMID: PMID: 17384219, 29171923, 15712271, Invitae). For these reasons, this variant has been classified as Pathogenic.

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