ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.1246G>A (p.Gly416Ser) (rs1592225112)

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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 RCV001000141 SCV001156624 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-08-08 criteria provided, single submitter clinical testing The ACVRL1 c.1246G>A; p.Gly416Ser variant is reported in the literature in individuals with HHT and has been reported to co-segregate with disease (Argyriou 2006, Lesca 2006, McDonald 2011). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 416 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict this variant to be deleterious. Additionally, this variant occurs in the last nucleotide of the exon and is predicted to impact splicing by significantly weakening the nearby canonical donor splice site (Alamut v.2.11). Based on available information, this variant is considered to be pathogenic. REFERENCES Argyriou L et al. Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia. Int J Mol Med. 2006 Apr;17(4):655-9. Lesca G et al. Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients. Hum Mutat. 2006 Jun;27(6):598. McDonald J et al. Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis. Clin Genet. 2011 Apr;79(4):335-44.

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