Submissions for variant NM_020988.3(GNAO1):c.692A>G (p.Tyr231Cys) (rs1057518678)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657944	SCV000779714	pathogenic	not provided	2018-05-18	criteria provided, single submitter	clinical testing	The Y231C variant in the GNAO1 gene has been reported as a de novo variant in multiple unrelated patients with early infantile epileptic encephalopathy (Talvik et al., 2015; Posey et al., 2017). Functional studies suggest that Y231C results in partial loss of function (Feng et al., 2017). The Y231C variant is not observed in large population cohorts (Lek et al., 2016). The Y231C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.
Baylor Genetics	RCV000414910	SCV000328761	likely pathogenic	Early infantile epileptic encephalopathy 17	2015-02-06	no assertion criteria provided	clinical testing	Our laboratory reported dual molecular diagnoses in GNAO1 (NM_138736.2, c.692A>G) and ACADM (NM_000016.4, c.287-2A>G and c.985A>G in trans) in one individual with reported features of medium chain acyl-CoA dehydrogenase deficiency, history of prematurity, developmental regression and seizures, non-ocular blindness. This variant was also found de novo in a second individual, a 1-year-old male with global delays, failure to thrive, hypotonia, seizures, dysmorphisms, microcephaly.
Pediatric Department, Peking University First Hospital	RCV001580371	SCV001486217	pathogenic	Early infantile epileptic encephalopathy 17; Neurodevelopmental disorder with involuntary movements	2021-02-03	no assertion criteria provided	clinical testing