ClinVar Miner

Submissions for variant NM_203290.4(POLR1C):c.835C>T (p.Arg279Trp) (rs141156009)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000382254 SCV000330026 pathogenic not provided 2016-12-27 criteria provided, single submitter clinical testing The R279W variant in the POLR1C gene has been reported previously in an individual with Treacher Collinssyndrome who was compound heterozygous for the R279W variant and a truncating variant (Dauwerse et al., 2011).The R279W variant was not observed with any significant frequency in approximately 6500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. The R279W variant is a non-conservative amino acid substitution, which occurs at aposition that is conserved across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. The functional importance of the R279 residue is supported by the presence of a different missensevariant (R279Q) reported in two affected siblings with TCS who harbored another POLR1C variant (phase notconfirmed), as well as in an unrelated individual with TCS who was compound heterozygous for R279Q and anonsense variant in POLR1C (Dauwerse et al., 2011). Therefore, we interpret R279W as a pathogenic variant.
MyeliNeuroGene Lab,McGill University Health Center Research Institute RCV000788033 SCV000924607 pathogenic Leukodystrophy, hypomyelinating, 11 criteria provided, single submitter research
OMIM RCV000023800 SCV000045091 pathogenic Mandibulofacial dysostosis, Treacher Collins type, autosomal recessive 2011-01-01 no assertion criteria provided literature only

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