ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.