ClinVar Miner

Submissions for variant NM_203290.4(POLR1C):c.836G>A (p.Arg279Gln) (rs191582628)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000023796 SCV000463455 likely pathogenic Treacher Collins syndrome 3 2017-04-27 criteria provided, single submitter clinical testing The POLR1C c.836G>A (p.Arg279Gln) missense variant has been reported in one study in which it was identified in a compound heterozygous state in three individuals, including two siblings, with Treacher Collins syndrome (Dauwerse et al. 2011). The p.Arg279Gln was also found in a heterozygous state in four unaffected family members. The variant was absent from 272 controls but is reported at a frequency of 0.00052 in the Latino population of the Exome Aggregation Consortium. Functional studies in HeLa cell lines stably expressing wild type or p.Arg279Gln-POLR1C demonstrated that the p.Arg279Gln variant did not affect polymerase assembly but did impair the targeting of the POLR1C protein to the nucleolus, the site of Pol I transcription (Thiffault et al. 2015). Based on the evidence, the p.Arg279Gln variant is classified as likely pathogenic for Treacher Collins syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513700 SCV000610900 pathogenic not provided 2017-06-01 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000023796 SCV000803555 pathogenic Treacher Collins syndrome 3 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Pathogenic, for Treacher Collins syndrome 3, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2-Supporting =>PM2 downgraded in strength to Supporting. PS3 => Well-established functional studies show a deleterious effect (PMID:29567474). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:21131976). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:21131976). PM5 => Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PMID:21131976). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
MyeliNeuroGene Lab,McGill University Health Center Research Institute RCV000788034 SCV000924608 pathogenic Leukodystrophy, hypomyelinating, 11 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513700 SCV001246211 pathogenic not provided 2016-10-01 criteria provided, single submitter clinical testing
OMIM RCV000023796 SCV000045087 pathogenic Treacher Collins syndrome 3 2011-01-01 no assertion criteria provided literature only

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.