ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.10204T>G (p.Cys3402Gly) (rs367543058)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147397 SCV000194776 pathogenic not provided 2013-12-02 criteria provided, single submitter clinical testing
Center for Genetic Medicine Research,Children's National Medical Center RCV000233916 SCV000265781 likely pathogenic Central core myopathy 2015-12-01 criteria provided, single submitter research
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000147397 SCV000335753 uncertain significance not provided 2015-10-19 criteria provided, single submitter clinical testing
GeneDx RCV000147397 SCV000521246 likely pathogenic not provided 2021-05-24 criteria provided, single submitter clinical testing Reported in a 6-year old with respiratory and feeding difficulties at birth, delayed gross motor milestones, and facial and proximal lower limb weakness who was also found to harbor a second pathogenic variant in RYR1 (Ghosh et al., 2020); Identified in two individuals with congenital fiber-type disproportion, including one individual who was also found to have a single heterozygous frameshift variant in the LAMA2 gene (Punetha et al., 2016); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23069638, 20583297, 27854218)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000401146 SCV000540253 uncertain significance not specified 2016-08-12 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Only reported in association with myopathy (congenital fiber type disproportion), in only 1 proband.
Invitae RCV000529599 SCV000659742 pathogenic RYR1-Related Disorders 2020-10-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 3402 of the RYR1 protein (p.Cys3402Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is present in population databases (rs367543058, ExAC 0.005%). This variant has been observed in combination with another RYR1 variant in individuals with autosomal recessive congenital myopathy (PMID: 20583297, Invitae). It has also been observed to segregate with disease in related individuals. In addition, this variant has been reported in the heterozygous state in individuals with congenital fiber type disproportion (CFTD) (PMID: 27854218); however, the role of this variant in autosomal dominant disease is unclear. ClinVar contains an entry for this variant (Variation ID: 42098). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000147397 SCV001246301 likely pathogenic not provided 2020-02-01 criteria provided, single submitter clinical testing
GeneReviews RCV000034925 SCV000058532 pathologic Congenital myopathy with fiber type disproportion 2013-04-11 no assertion criteria provided curation Converted during submission to 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.