Submissions for variant NM_000540.3(RYR1):c.12458T>G (p.Val4153Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004805347	SCV005425347	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2024-05-09	criteria provided, single submitter	clinical testing	This missense variant replaces valine with glycine at codon 4153 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 1/251142 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV005230797	SCV005877900	uncertain significance	not provided	2024-03-22	criteria provided, single submitter	clinical testing	The RYR1 c.12458T>G; p.Val4153Gly variant (rs1437917324), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only found on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.785). Due to limited information, the clinical significance of this variant is uncertain at this time.