Rhotekin (RTKN2) was evaluated for autosomal recessive dilated cardiomyopathy (DCM). RTKN2 belongs to a group of proteins containing a Rho-binding domain targeted by Rho-GTPases and is critical in lymphocyte development and function (Collier F et al. 2004; PMID: 15504364). To date, it has not been associated with any type of cardiovascular disease. There is a single study that has reported the RTKN2 c.1430_1433dup p.His478GlnfsTer16 variant in homozygosity in a case of DCM from Pakistan (Shakeel M et al. 2018; PMID: 29886034). This study provides no family or clinical data and the proband in question was found to carry two more potentially deleterious variants in other genes. Furthermore, p.His478GlnfsTer16 has a frequency of over 2.5% in the South Asian population in the 1000 Genomes Project phase 3 and ExAC datasets. There are no other genetic or functional studies implicating RTKN2 with DCM. Based on this evidence, the approved classification for this gene is No known disease relationship. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on 12/13/2024 (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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