Submissions for variant NM_000540.3(RYR1):c.14421CTT[2] (p.Phe4810del)

dbSNP: rs1555803810

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520157	SCV000617754	uncertain significance	not provided	2018-08-07	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the RYR1gene. The c.14427_14429delCTT variant has been reported previously (using alternative nomenclature) in trans with a missense variant in an individual with a RYR1-related myopathy (Bharucha-Goebel et al., 2013) The c.14427_14429delCTT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.14427_14429delCTT variant results in an in-frame deletion of one amino acid, denoted p.Phe4810del. In silico analysis predicts this variant is probably damaging to the protein structure/function. The deleted amnio acid occurs at a position that is conserved. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000804563	SCV000944479	uncertain significance	RYR1-related disorder	2024-01-22	criteria provided, single submitter	clinical testing	This variant, c.14427_14429del, results in the deletion of 1 amino acid(s) of the RYR1 protein (p.Phe4810del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal recessive central core disease (PMID: 23553484). This variant is also known as p.Phe4808del. ClinVar contains an entry for this variant (Variation ID: 449523). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000520157	SCV001371008	likely pathogenic	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796225	SCV005416214	uncertain significance	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; King Denborough syndrome		criteria provided, single submitter	clinical testing	PM2_Supporting+PP4+PM4