ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1055C>A (p.Ala352Asp) (rs1085307415)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507211 SCV000602431 pathogenic not specified 2017-01-04 criteria provided, single submitter clinical testing
Invitae RCV000525054 SCV000639386 likely pathogenic Hereditary hemorrhagic telangiectasia type 2 2017-06-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 352 of the ACVRL1 protein (p.Ala352Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency) . This variant has been reported in the literature in individuals with hereditary haemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PMID: 19357124, 16690726) and individuals with suspected HHT (PMID: 21158752). 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 missense change is absent from the population but has been reported in several affected individuals and families. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Medical & Molecular Genetics Group,University of Lincoln RCV000488852 SCV000576329 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia no assertion criteria provided literature only

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