Submissions for variant NM_000540.3(RYR1):c.14283G>A (p.Pro4761=)

gnomAD frequency: 0.00005  dbSNP: rs201157293

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000345135	SCV000413020	uncertain significance	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000401414	SCV000413021	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000310165	SCV000413022	uncertain significance	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000339321	SCV000413023	uncertain significance	Congenital multicore myopathy with external ophthalmoplegia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000556274	SCV000659844	likely benign	RYR1-related disorder	2024-11-06	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003133228	SCV003813035	uncertain significance	not provided	2019-07-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000401414	SCV004358225	likely benign	Malignant hyperthermia, susceptibility to, 1	2022-11-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000401414	SCV004818858	likely benign	Malignant hyperthermia, susceptibility to, 1	2023-10-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003133228	SCV005093449	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RYR1: BP4, BP7