ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.651G>A (p.Trp217Ter)

dbSNP: rs1592223399
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000811840 SCV000952127 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2022-09-03 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp217*) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 655621). This premature translational stop signal has been observed in individuals with hereditary haemorrhagic telangiectasia (PMID: 16752392, 25970827).
Ambry Genetics RCV002363104 SCV002659313 pathogenic Cardiovascular phenotype 2021-05-14 criteria provided, single submitter clinical testing The p.W217* pathogenic mutation (also known as c.651G>A), located in coding exon 5 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 651. This changes the amino acid from a tryptophan to a stop codon within coding exon 5. This nonsense mutation (also seen as c.650G>A) was first described in an individual with epistaxis and telangiectasias (Bossler AD et al. Hum Mutat. 2006;27(7):667-75). It has also been reported in hereditary hemorrhagic telangiectasia families from Italy and Norway (Olivieri C, J. Hum. Genet. 2007 ; 52(10):820-9. Heimdal K, Clin. Genet. 2015 May). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV005235484 SCV005882687 pathogenic Hereditary hemorrhagic telangiectasia 2024-07-11 criteria provided, single submitter clinical testing PVS1, PS4, PM2

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