ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8309T>C (p.Ile2770Thr)

gnomAD frequency: 0.00004  dbSNP: rs397516550
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036796 SCV000060451 uncertain significance not specified 2011-09-27 criteria provided, single submitter clinical testing The Ile2770Thr variant (RYR2) has not been reported in the literature and has no t been previously detected by our laboratory. Isoleucine (Ile) at position 2770 is not completely conserved in evolutionarily distant species (zebrafish carries a difference amino acid), raising the possibility that this change may be toler ated. Computational predications are mixed, though the accuracy of these tools i s unknown. In summary, additional data is needed to clarify the significance of this variant.
Illumina Laboratory Services, Illumina RCV001095886 SCV001252063 uncertain significance Arrhythmogenic right ventricular dysplasia 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001095887 SCV001252064 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Diagnostics, LLC DBA Color Health RCV001175860 SCV001339639 uncertain significance Cardiomyopathy 2023-04-07 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has been identified in 5/185468 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002496576 SCV002814096 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-11-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001095887 SCV003439854 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2025-01-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996303 SCV004823276 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-01-11 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/185468 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004017312 SCV004849270 uncertain significance Cardiovascular phenotype 2019-10-08 criteria provided, single submitter clinical testing The c.8309T>C (p.I2770T) alteration is located in exon 56 (coding exon 56) of the RYR2 gene. This alteration results from a T to C substitution at nucleotide position 8309, causing the isoleucine (I) at amino acid position 2770 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.