ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7298T>C (p.Leu2433Pro)

dbSNP: rs1600822174
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
Cirak Lab, University Hospital Cologne RCV000855484 SCV000996614 likely pathogenic Fetal akinesia deformation sequence 1; Arthrogryposis multiplex congenita 2019-06-28 criteria provided, single submitter research
CeGaT Center for Human Genetics Tuebingen RCV002275162 SCV002563529 uncertain significance not provided 2021-08-01 criteria provided, single submitter clinical testing
Invitae RCV003117621 SCV003790428 likely pathogenic RYR1-Related Disorders 2022-05-31 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2433 of the RYR1 protein (p.Leu2433Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive centronuclear myopathy (PMID: 31680123). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 692292). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.