Submissions for variant NM_000540.3(RYR1):c.4343G>A (p.Trp1448Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003592030	SCV004112771	likely pathogenic	RYR1-related disorder	2023-03-07	criteria provided, single submitter	clinical testing	The RYR1 c.4343G>A variant is predicted to result in premature protein termination (p.Trp1448*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in RYR1 are expected to be pathogenic for autosomal recessive RYR1-related disorders. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003592030	SCV004262197	pathogenic	RYR1-related disorder	2023-12-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp1448*) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2633558). For these reasons, this variant has been classified as Pathogenic.