Submissions for variant NM_001036.6(RYR3):c.9143G>T (p.Arg3048Leu)

dbSNP: rs139568967

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000553337	SCV000634906	benign	Epileptic encephalopathy	2022-11-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586771	SCV005076400	likely benign	not specified	2024-04-26	criteria provided, single submitter	clinical testing	Variant summary: RYR3 c.9143G>T (p.Arg3048Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 248290 control chromosomes, predominantly at a frequency of 0.0094 within the East Asian subpopulation in the gnomAD database, including 6 homozygotes, strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.9143G>T in individuals affected with Congenital Myopathy 20 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 461980). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003925624	SCV004740834	benign	RYR3-related disorder	2019-12-09	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).