Submissions for variant NM_212472.2(PRKAR1A):c.1102C>T (p.Arg368Ter) (rs387906692)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760318	SCV000890174	pathogenic	not provided	2018-07-10	criteria provided, single submitter	clinical testing	The R368X variant in the PRKAR1A gene has been reported previously as a de novo finding in multiple unrelated individuals with a variety of clinical features, including acrodysostosis, brachydactyly, short stature, and hormone resistance (Linglart et al., 2011; Michot et al., 2012; Pereda et al., 2018). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies demonstrated that R368X impairs the ability of cAMP to dissociate the regulatory and catalytic subunits of PKA, consistent with a gain of function effect (Linglart et al., 2011; Rhayem et al., 2015). The R368X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R368X as a pathogenic variant.
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals	RCV000022791	SCV001156417	pathogenic	Acrodysostosis 1 with or without hormone resistance	2019-02-01	criteria provided, single submitter	clinical testing
OMIM	RCV000022791	SCV000044080	pathogenic	Acrodysostosis 1 with or without hormone resistance	2012-04-06	no assertion criteria provided	literature only