ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.693CTC[1] (p.Ser233del)

dbSNP: rs387906391
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230219 SCV000282681 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2023-12-16 criteria provided, single submitter clinical testing This variant, c.696_698del, results in the deletion of 1 amino acid(s) of the ACVRL1 protein (p.Ser233del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hereditary hemorrhagic telangiectasia (HHT) (PMID: 8640225, 15024723, 16752392, 21158752; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 236552). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506933 SCV000602394 pathogenic not specified 2016-08-16 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001507805 SCV001713598 pathogenic not provided 2020-01-28 criteria provided, single submitter clinical testing PP1_Strong, PS4, PP4, PM4, PM2
Ambry Genetics RCV002372240 SCV002668283 pathogenic Cardiovascular phenotype 2022-12-13 criteria provided, single submitter clinical testing The c.696_698delCTC pathogenic mutation (also known as p.S233del) is located in coding exon 5 of the ACVRL1 gene. This pathogenic mutation results from an in-frame CTC deletion at nucleotide positions 696 to 698. This results in the in-frame deletion of a serine at codon 233. This pathogenic mutation segregated with disease in a large family affected with hereditary hemorrhagic telangiectasia (HHT); however, there were a few unaffected carriers, which was attributed to incomplete penetrance (Johnson DW et al. Nat. Genet., 1996 Jun;13:189-95). This pathogenic mutation was also observed in an individual that presented with epistaxis, telangiectasias, and a family history of HHT (Bossler AD et al. Hum. Mutat., 2006 Jul;27:667-75). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
GeneDx RCV001507805 SCV002757188 pathogenic not provided 2022-11-25 criteria provided, single submitter clinical testing In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10767348, 16752392, 21158752, 9245985, 15266205, 8640225, 15024723)
OMIM RCV000230219 SCV000028938 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 1996-06-01 no assertion criteria provided literature only

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