ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.677T>A (p.Val226Glu) (rs1565593639)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755784 SCV000883356 likely pathogenic not provided 2017-06-09 criteria provided, single submitter clinical testing The ACVRL1 c.677T>A; p.Val226Glu variant has been reported in the literature to segregate with disease in a family affected with hereditary hemorrhagic telangiectasia (HHT) (Richards-Yutz 2010). In addition, two other variants at this codon (p.Val226Leu, p.Val226Met) have been associated with HHT or pulmonary arterial hypertension (PAH) (Piao 2016, Torring 2014). The p.Val226Glu variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database). The valine at codon 226 is a highly conserved residue in the ATP-binding site of the protein kinase domain (InterPro), and computational algorithms (SIFT, PolyPhen2, MutationTaster, Align GVGD) predict this variant to be damaging to the protein. Taken together, this variant is considered likely pathogenic. REFERENCES Piao C et al. Identification of multiple ACVRL1 mutations in patients with pulmonary arterial hypertension by targeted exome capture. Clin Sci (Lond). 2016 Sep 1;130(17):1559-69. Richards-Yutz J et al. Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul;128(1):61-77. Torring PM et al. National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet. 2014 Aug;86(2):123-33.

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