ROBO1 was first reported in relation to autosomal dominant congenital heart disease in 2017 (Kruszka et al., PMID: 28592524). Two de novo truncation variants that have been reported in 2 probands in 1 publications (PMID: 28592524) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (fly and mouse expression-level data; and fly and mouse models) (PMIDs: 23255421, 20941780, 23328398, 25691540, 16360689, 18663139, 23825967, 21385766, 28592524). The mouse models have somewhat variable phenotypes but generally indicate increased rates of ventricular septal defects and outflow tract anomalies in Robo1 null mice. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 9/3/2024 (SOP Version 10).
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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