ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1768G>T (p.Asp590Tyr)

gnomAD frequency: 0.00004  dbSNP: rs552148844
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001216117 SCV001387894 uncertain significance RYR1-related disorder 2022-05-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 590 of the RYR1 protein (p.Asp590Tyr). This variant is present in population databases (rs552148844, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 945468). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002504261 SCV002814474 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-08-06 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010708 SCV004822298 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with tyrosine at codon 590 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 RYR1-related disorders in the literature. This variant has been identified in 20/282768 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 RCV004659401 SCV005161790 uncertain significance Inborn genetic diseases 2024-03-20 criteria provided, single submitter clinical testing The c.1768G>T (p.D590Y) alteration is located in exon 16 (coding exon 16) of the RYR1 gene. This alteration results from a G to T substitution at nucleotide position 1768, causing the aspartic acid (D) at amino acid position 590 to be replaced by a tyrosine (Y). 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.