ClinVar Miner

Submissions for variant NM_001036.6(RYR3):c.4297A>G (p.Thr1433Ala)

gnomAD frequency: 0.00007  dbSNP: rs201020040
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001211151 SCV001382676 uncertain significance Epileptic encephalopathy 2024-06-05 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1433 of the RYR3 protein (p.Thr1433Ala). This variant is present in population databases (rs201020040, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 941374). 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 not expected to disrupt RYR3 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV004659393 SCV005158878 uncertain significance not specified 2024-04-06 criteria provided, single submitter clinical testing The c.4297A>G (p.T1433A) alteration is located in exon 32 (coding exon 32) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 4297, causing the threonine (T) at amino acid position 1433 to be replaced by an alanine (A). 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.