Submissions for variant NM_000540.3(RYR1):c.9148G>A (p.Val3050Ile)

gnomAD frequency: 0.00014  dbSNP: rs200797340

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000381209	SCV000412620	likely benign	Multiminicore myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000289050	SCV000412621	likely benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000346443	SCV000412622	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000384648	SCV000412623	likely benign	Malignant hyperthermia of anesthesia	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655514	SCV000777445	likely benign	RYR1-related disorder	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001660679	SCV001872475	uncertain significance	not provided	2021-12-20	criteria provided, single submitter	clinical testing	Observed in an individual with centronuclear myopathy through a neuromuscular disorders next-generation sequencing panel (Gonzalez-Quereda et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32403337, 12668474)
Revvity Omics, Revvity	RCV001660679	SCV003814428	uncertain significance	not provided	2023-04-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995872	SCV004820948	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2024-08-13	criteria provided, single submitter	clinical testing	This missense variant replaces valine with isoleucine at codon 3050 of the RYR1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is has been observed in individuals affected with other condition(s) (PMID: 32403337). This variant has been identified in 39/282718 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.
CeGaT Center for Human Genetics Tuebingen	RCV001660679	SCV005330733	uncertain significance	not provided	2024-08-01	criteria provided, single submitter	clinical testing	RYR1: PP4
Fulgent Genetics, Fulgent Genetics	RCV005018684	SCV005647475	uncertain significance	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; King Denborough syndrome	2024-04-05	criteria provided, single submitter	clinical testing