Submissions for variant NM_000540.3(RYR1):c.5691_5720del (p.Glu1898_Glu1907del)

dbSNP: rs1229062996

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003063524	SCV003457606	uncertain significance	RYR1-related disorder	2021-12-31	criteria provided, single submitter	clinical testing	The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.5691_5720del, results in the deletion of 10 amino acid(s) of the RYR1 protein (p.Glu1898_Glu1907del), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with RYR1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
All of Us Research Program, National Institutes of Health	RCV004009349	SCV004825518	uncertain significance	Malignant hyperthermia, susceptibility to, 1	2024-03-24	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 10 amino acids in the RYR1 protein. 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 1/31374 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.