ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.72_79del (p.Lys25fs) (rs1592221459)

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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 RCV001000940 SCV001158039 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-12-04 criteria provided, single submitter clinical testing The ACVRL1 c.72_79delGAAGCCGT; p.Lys25fs variant, to our knowledge, is not described in the medical literature or in gene-specific databases. It is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 8 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) and are considered pathogenic (Abdalla 2003, Abdalla 2005, Assis 2007, Bayrak-Toydemir 2006, Lesca 2004). Based on available information, the p.Lys25fs variant is considered pathogenic. REFERENCES Abdalla S et al. Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur J Hum Genet. 2003; 11(4):279-87. Abdalla S et al. Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia. Hum Mutat. 2005; 25(3):320-1. Assis A et al. Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients. J Hum Genet. 2007;52(3):237-43. Bayrak-Toydemir P et al. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A. 2006 Mar 1;140(5):463-70. Lesca G et al. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004; 23(4):289-99.

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