ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000005.9) (NC_000005.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
24038909 Revencu et al., 2013 reported mutations in RASA1 in 68 index patients with capillary malformation-arteriovenous malformation (CM-AVM). 70 additional family members were found to have the familial RASA1 mutation as well. Of the 138 total, 136 exhibited capillary malformations. 58 different mutations were reported, 43 novel and 15 previously described in the literature and most are consistent with loss -of-function and haploinsufficiency. Mutations were reported across the gene and no genotype/phenotype correlation was identified.
29891884 An additional 60 deleterious variants (including 5 large deletions), and 9 variants of unknown significance were reported by Wooderchak-Donahue 2017 (PMID 29891884) from a cohort of 281 unrelated individuals submitted for clinical RASA1 testing. Though detailed phenotype information was not provided for all patients found to have RASA1 variants, 75% were reported to have capillary malformations and those without reported capillary malformations were reported to have arteriovenous malformations.

Haploinsufficiency phenotype comments:

Per OMIM: "Capillary malformation-arteriovenous malformation-1 is an autosomal dominant disorder characterized by atypical capillary malformations (CMs), often in association with fast-flow vascular malformations, including arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs), and Parkes Weber syndrome (PKWS). "

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity