ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys)

gnomAD frequency: 0.00006  dbSNP: rs140812286
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670706 SCV000795597 uncertain significance GRACILE syndrome 2017-11-09 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000778591 SCV000914898 uncertain significance Mitochondrial complex III deficiency nuclear type 1 2017-05-22 criteria provided, single submitter clinical testing The BCS1L c.217C>T (p.Arg73Cys) variant has been reported in two studies in the same individual with mitochondrial respiratory chain complex III deficiency in a compound heterozygous state with another missense variant (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The p.Arg73Cys variant was absent from 210 control alleles, but is reported at a frequency of 0.00315 in the Ashkenazi Jewish population of the Genome Aggregation Database. The Arg73 residue is conserved across multiple species. Patient fibroblasts showed 30% residual enzyme activity and 50% maximum respiration rate compared to wild type (Invernizzi et al. 2012). Growth complementation studies in yeast showed that the p.Arg73Cys variant alone was insufficient to cause a growth defect, but in the presence of the other missense variant from the compound heterozygous patient, growth was significantly reduced compared to wild type. A similar result was obtained looking at the mitochondrial cytochrome profile and respiration activity (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The evidence for this variant is limited. The p.Arg73Cys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for mitochondrial respiratory chain complex III deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Center for Human Genetics Tuebingen RCV001171821 SCV001334690 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
Invitae RCV001171821 SCV001689654 likely benign not provided 2021-11-13 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.