Submissions for variant NM_000540.3(RYR1):c.14555A>G (p.Tyr4852Cys)

dbSNP: rs886042826

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655579	SCV000777510	pathogenic	RYR1-related disorder	2021-06-24	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with central core myopathy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 284245). 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 4852 of the RYR1 protein (p.Tyr4852Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine.
PreventionGenetics, part of Exact Sciences	RCV000721382	SCV000852430	likely pathogenic	not provided	2021-08-25	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000721382	SCV000336785	uncertain significance	not provided	2015-11-09	flagged submission	clinical testing