ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.12083C>T (p.Ser4028Leu) (rs794728696)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210653 SCV000262901 uncertain significance Inborn genetic diseases 2013-11-04 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000721259 SCV000335362 uncertain significance not provided 2015-09-25 criteria provided, single submitter clinical testing
Invitae RCV000542897 SCV000659783 pathogenic RYR1-Related Disorders 2020-02-21 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 4028 of the RYR1 protein (p.Ser4028Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with autosomal dominant congenital myopathy and to segregate with congenital myopathy in a family (PMID: 25987458, 27447704, Invitae). ClinVar contains an entry for this variant (Variation ID: 201152). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000721259 SCV000852280 uncertain significance not provided 2013-12-30 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.