FGFR1 has been described in relation to autosomal dominant Hartsfield Syndrome (HS) as early as 2013 by Simonis et al. (PMID: 23812909). HS is characterized by the co-occurrence of holoprosencephaly, ectrodactyly, and cleft lip and palate. At least 17 unique missense variants have been reported in the literature. Evidence supporting this gene-disease relationship includes case-level data, of 18 probands from 9 publications (PMIDs: 31512363, 27790375, 26931467, 27170295, 32373773, 30787447, 23812909, 27363716, 28825856). A mouse model was evaluated for this gene-disease relationship but was not counted towards the final score as it does not recapitulate the disease specific phenotypes (Calvert et al. 2011; PMID: 21479780). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 2/18/2021. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
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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