Submissions for variant NM_001035.3(RYR2):c.10190G>A (p.Arg3397His)

dbSNP: rs753630324

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001190381	SCV001357844	uncertain significance	Cardiomyopathy	2020-11-03	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 3397 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in one individual affected with eccentric left ventricular hypertrophy (PMID: 28123168). This variant has also been reported in one individual affected with long QT syndrome; however, the individual's mother who also carried the variant didn't show the phenotype (PMID: 32681117). This variant has been identified in 3/278184 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002559178	SCV003523635	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-04-30	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004803541	SCV005428040	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia	2024-06-11	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 3397 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in one individual affected with eccentric left ventricular hypertrophy (PMID: 28123168). This variant has also been reported in one individual affected with long QT syndrome; however, the individual's mother who also carried the variant didn't show the phenotype (PMID: 32681117). This variant has been identified in 3/278184 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.