There have been multiple reported cases in the literature showing that RASA1 variants can cause cardiovascular anomalies such as capillary malformation-arteriovenous malformation syndrome (CM-AVM)(Ilari, Agosta, & Bacino, 2016; Macmurdo et al., 2016). These studies suggest that these patients may possess clinical features of Noonan syndrome (NS). However, patients with additional phenotypes such as hypotonia and severe ID all possess secondary causes of disease apart from RASA1 variation. Therefore, there is no convincing genetic evidence that supports the association of RASA1 and NS. In fact, RASA1 should most likely only be associated with cardiovascular anomalies. RASA1’s association with NS is Disputed. The ClinGen RASopathy Expert Panel found no evidence associating RASA1 with cardiofaciocutaneous syndrome, Costello syndrome, NS with loose anagen hair, or NS with multiple lentigines. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 6/7/18 (SOP Version 5).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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