SRCAP was first reported in relation to autosomal dominant Floating Harbor Syndrome (FHS) in 2012 (Hood et al., PMID: 22265015). A rare genetic disorder, FHS is characterized by short stature, delayed bone age, delayed speech development, and distinctive facial features – the face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. Additional phenotypes including mild to moderate intellectual disability have also been reported. The specific phenotypes and severity of FHS vary greatly from one person to another and also by age. Fourteen variants (frameshift (9) and nonsense (5)) mostly de novo (9), reported in 14 probands in 5 publications are included in this curation (PMIDs: 22265015, 22965468, 25433523, 23621943, 30425916). Two of the variants, c.7330C>T (p.Arg2444*) and c.7303C>T (p.Arg2435*) on exon 34, are recurrent and have been reported in sixteen and ten unrelated individuals, respectively (PMID: 22265015, 22965468, 25433523, 30425916, 23621943). The mechanism of pathogenicity is reported as haploinsufficiency. While more evidence is available in the literature, the maximum score for genetic evidence (12 points) has been reached. In summary, there is definitive evidence to support the relationship between SRCAP and Floating Harbor Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism expert panel on August 1, 2023 (SOP Version 9).
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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