ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.2682G>A (p.Pro894=) (rs919322708)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497675 SCV000589646 likely pathogenic not provided 2015-12-17 criteria provided, single submitter clinical testing In silico models predict the c.2682 G>A variant damages or destroys the natural splice donor site at the exon 21/intron 21 junction, suggesting this variant leads to abnormal gene splicing; however, in the absence of mRNA studies the actual effect of c.2682 G>A is uncertain. This variant is not observed in 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.2682 G>A variant is a strong candidate to be pathogenic, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000542169 SCV000659900 uncertain significance RYR1-Related Disorders 2017-07-25 criteria provided, single submitter clinical testing This sequence change affects codon 894 of the RYR1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RYR1 protein. This variant also falls at the last nucleotide of exon 21 of the RYR1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with multiminicore disease (PMID: 25960145). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on RNA splicing and protein function. It has been classified as a Variant of Uncertain Significance.
PreventionGenetics RCV000497675 SCV000852542 uncertain significance not provided 2016-12-19 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.