LEFTY2 was first reported in relation to autosomal dominant congenital heart disease in 1999 (Kosaki et al., PMID: 10053005). Three variants (a missense, a nonsense, and a chromosomal segment deletion) that have been reported in three probands in two publications (PMIDs: 10053005, 25516202) are included in this curation. However, none were scored. The missense and nonsense mutations are too frequent in the general population, and the chromosomal segment deletion included other CHD-associated genes. The only experimental evidence, a mouse model, was not scored due to the lack of scorable genetic evidence and only a low portion of mice exhibiting cardiac anomalies (PMID: 11703930). In summary, the evidence supporting the relationship between LEFTY2 and autosomal dominant congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role LEFTY2 plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 2/6/2022 (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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