ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.693CTC[1] (p.Ser233del) (rs387906391)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230219 SCV000282681 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2020-06-29 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 6 of the ACVRL1 mRNA (c.696_698delCTC). This leads to the deletion of 1 amino acid residue(s) in the ACVRL1 protein (p.Ser233del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hereditary hemorrhagic telangiectasia (HHT) in a large multigenerational family and to be present in other independent HHT cases (PMID: 8640225, 15024723, 16752392, 21158752). This variant is also known as DS232 in the literature. ClinVar contains an entry for this variant (Variation ID: 8245). The serine residue deleted in this variant is located in the ATP binding site of the kinase domain and is conserved in most of the type I receptors of the TGF-beta superfamily indicating that this residue may be important for protein function (PMID: 10767348, 15024723). However, this has not been confirmed by published functional studies. In summary, this is a rare variant that has been found in HHT affected individuals and has been shown to segregate with these disease in a large family. For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506933 SCV000602394 pathogenic not specified 2016-08-16 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001507805 SCV001713598 pathogenic not provided 2020-01-28 criteria provided, single submitter clinical testing PP1_Strong, PS4, PP4, PM4, PM2
OMIM RCV000230219 SCV000028938 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 1996-06-01 no assertion criteria provided literature only

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