ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.601C>T (p.Gln201Ter) (rs1318446539)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627226 SCV000748215 pathogenic not provided 2018-04-16 criteria provided, single submitter clinical testing The Q201X variant in the ACVRL1 gene has been reported in an individual fulfilling three Curacao criteria for HHT due to a history of epistaxis, telangiectasias and a family history of HHT (Richards-Yutz et al., 2010). It has also been reported in another individual referred to an outside laboratory for HHT genetic testing, although no further clinical details were available (McDonald et al., 2011). Q201X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the ACVRL1 gene have been reported in the Human Gene Mutation Database in association with HHT (Stenson et al., 2014). Furthermore, the Q201X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016).
Invitae RCV000640438 SCV000762029 pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln201*) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with hereditary hemorrhagic telangiectasia (PMID: 21158752). Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000640438 SCV000893305 pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000640438 SCV001158597 pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-10-08 criteria provided, single submitter clinical testing The ACVRL1 c.601C>T; p.Gln201Ter variant, is reported in the literature in multiple individuals affected with hereditary hemorrhagic telangiectasia (McDonald 2011, Richards-Yutz 2010). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 523779), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Gln201Ter variant is considered to be pathogenic. References: 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. Richards-Yutz J et al. Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul;128(1):61-77.

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