Submissions for variant NM_020247.5(COQ8A):c.811C>T (p.Arg271Cys) (rs145034527)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000388682	SCV000355247	uncertain significance	Autosomal recessive cerebellar ataxia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000416392	SCV000355248	likely pathogenic	Coenzyme Q10 deficiency, primary, 4	2018-05-07	criteria provided, single submitter	clinical testing	The ADCK3 c.811C>T (p.Arg271Cys) missense variant has been reported in three studies in which it is found in at least four individuals with ataxia including in a homozygous state in one individual, in a compound heterozygous state in at least three individuals including two siblings (Horvath et al. 2012; Mignot et al. 2013; Bargiela et al. 2015). The p.Arg271Cys variant was absent from 100 healthy controls and is reported at a frequency of 0.00139 in the European (Finnish) population of the Exome Aggregation Consortium. The Arg271 residue is conserved across vertebrates. Based on the evidence, the p.Arg271Cys variant is classified as likely pathogenic for coenzyme Q10 deficiency, spinocerebellar ataxia type. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx	RCV000493536	SCV000581788	likely pathogenic	not provided	2018-04-16	criteria provided, single submitter	clinical testing	The R271C variant has been reported previously in the homozygous state or in conjunction with another ADCK3 variant in individuals with ADCK3-related disorders including juvenile or adult onset cerebellar ataxia and childhood onset epileptic encephalopathy (Horvath et al., 2012; Mignot et al., 2013; Bargiela et al., 2015; Thevenon et al., 2016). The 271C variant is observed in 20/25,144 (0.08%) alleles from individuals of Finnish background (Lek et al., 2016). This 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.
Genetic Services Laboratory,University of Chicago	RCV000416392	SCV000593039	likely pathogenic	Coenzyme Q10 deficiency, primary, 4	2016-09-06	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000493536	SCV000701080	uncertain significance	not provided	2016-10-05	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000416392	SCV000965805	uncertain significance	Coenzyme Q10 deficiency, primary, 4	2014-01-01	criteria provided, single submitter	clinical testing
GeneReviews	RCV000416392	SCV000494104	pathogenic	Coenzyme Q10 deficiency, primary, 4	2016-06-07	no assertion criteria provided	literature only