ClinVar Miner

Submissions for variant NM_203290.4(POLR1C):c.916_920del (p.Tyr306fs)

dbSNP: rs767639108
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MyeliNeuroGene Lab, McGill University Health Center Research Institute RCV000788035 SCV000924610 pathogenic Hypomyelinating leukodystrophy 11 criteria provided, single submitter research
Fulgent Genetics, Fulgent Genetics RCV002487617 SCV002791382 pathogenic Treacher Collins syndrome 3; Hypomyelinating leukodystrophy 11 2022-01-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003727826 SCV004535416 pathogenic not provided 2023-08-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 635151). This premature translational stop signal has been observed in individual(s) with leukodystrophy and/or Treacher Collins syndrome (PMID: 30957429, 32042905). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs767639108, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Tyr306Leufs*4) in the POLR1C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the POLR1C protein.
GeneDx RCV003727826 SCV005327835 likely pathogenic not provided 2023-07-25 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34426522, 610060, 30957429, 33149276, 32042905)

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