Submissions for variant NM_000540.3(RYR1):c.14416A>G (p.Asn4806Asp)

dbSNP: rs886039586

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255902	SCV000322471	pathogenic	not provided	2019-12-11	criteria provided, single submitter	clinical testing	Published functional studies demonstrate an impairment of the calcium release channel function and regulation at the Asn4806 residue (Du et al., 1998); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22473935, 28818389, 27234031, 9822655)
PreventionGenetics, part of Exact Sciences	RCV000255902	SCV000852410	likely pathogenic	not provided	2015-08-07	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000784911	SCV000923452	pathogenic	not specified	2024-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047738	SCV001211718	pathogenic	RYR1-related disorder	2022-10-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function. ClinVar contains an entry for this variant (Variation ID: 265505). This missense change has been observed in individuals with autosomal recessive RYR1-related conditions (PMID: 22473935, 25960145, 27234031, 28818389). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 4806 of the RYR1 protein (p.Asn4806Asp).
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814134	SCV001755574	pathogenic	Abnormality of the musculature	2021-07-10	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV000255902	SCV002501371	likely pathogenic	not provided	2021-05-16	criteria provided, single submitter	clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003761884	SCV004543859	pathogenic	RYR1-related myopathy	2023-01-16	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000255902	SCV000331383	uncertain significance	not provided	2015-10-19	flagged submission	clinical testing