Submissions for variant NM_000540.3(RYR1):c.4911G>A (p.Ala1637=)

gnomAD frequency: 0.00018  dbSNP: rs370350821

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000487624	SCV000575171	uncertain significance	not provided	2019-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000487624	SCV000983618	likely benign	not provided	2020-09-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083520	SCV001002809	likely benign	RYR1-related disorder	2025-01-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001122863	SCV001281633	uncertain significance	Congenital multicore myopathy with external ophthalmoplegia	2018-01-12	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	RCV001128563	SCV001288028	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2018-01-12	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.
Revvity Omics, Revvity	RCV000487624	SCV003814967	uncertain significance	not provided	2019-11-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003993983	SCV004813649	likely benign	not specified	2024-02-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV001083520	SCV000852655	likely benign	RYR1-related disorder	2019-09-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).