ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.13513G>C (p.Asp4505His) (rs150396398)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000584956 SCV000614901 uncertain significance not provided 2018-01-15 criteria provided, single submitter clinical testing
Biesecker Lab/Human Development Section,National Institutes of Health RCV000180740 SCV000265748 benign Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
CSER_CC_NCGL; University of Washington Medical Center RCV000148789 SCV000190527 likely benign Myopathy, progressive axial with cataracts 2014-06-01 no assertion criteria provided research
CSER_CC_NCGL; University of Washington Medical Center RCV000211491 SCV000212212 likely benign Malignant hyperthermia 2015-03-11 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000584956 SCV000692966 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415198 SCV000492937 uncertain significance Congenital muscular dystrophy; Generalized muscle weakness; EMG: myopathic abnormalities; Dysplasia of acetabulum 2014-11-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000584956 SCV000233225 uncertain significance not provided 2016-07-22 criteria provided, single submitter clinical testing
GeneDx RCV000433256 SCV000514428 likely benign not specified 2018-03-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
GenomeConnect, ClinGen RCV000287126 SCV000607351 not provided Malignant hyperthermia susceptibility no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Illumina Clinical Services Laboratory,Illumina RCV000287126 SCV000412979 likely benign Malignant hyperthermia susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000584956 SCV000697407 uncertain significance not provided 2016-10-19 criteria provided, single submitter clinical testing Variant summary: The RYR1 c.13513G>C (p.Asp4505His) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant. This variant was found in 281/46630 control chromosomes at a frequency of 0.0060262, which is approximately 69 times the estimated maximal expected allele frequency of a pathogenic RYR1 variant (0.0000875) based on the prevalence of Malignant Hyperthermia Susceptibility, suggesting this variant may be a likely benign polymorphism. However, phenotypes associated with this gene can be silent, generally have a late onset and penetrance of pathogenic variants in this gene are not complete; therefore, the frequency data alone cannot rule out pathogenicity or modifier role. This variant has been reported in patients with Idiopathic hyperCKemia, Malignant Hyperthermia Susceptibility, congenital myopathy, RYR1-related late-onset axial myopathy and atrioventricular septal defect (Malandrini_2008, Groom_2011, Klein_2012, Maggi_2013, Lseth_2013, Klingler_2014, Gillies_2015, Priest_2016); however no strong evidences of pathogenicity were found in these studies. This variant was found to cause modest increase in caffeine sensitivity as compared to wild type, and to further enhance such sensitivity when present in cis or trans with another variant p.R3983C (Groom_2011). A publication reviews available publications including their own and based on the equivocal data presented in the multiple published reports and the low frequency in the EVS, authors categorized the variant as a variant of unknown significance (Gonsalves_2013). Multiple clinical laboratories in ClinVar have classified this variant as VUS/likely benign/benign. Taken together, this variant is currently classified as variant of uncertain significance.
Invitae RCV000552343 SCV000659821 benign RYR1-Related Disorders 2018-01-08 criteria provided, single submitter clinical testing
PreventionGenetics RCV000584956 SCV000852353 uncertain significance not provided 2018-03-29 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.