Submissions for variant NM_016599.5(MYOZ2):c.688C>T (p.Arg230Trp)

dbSNP: rs372215131

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154787	SCV000204467	uncertain significance	not specified	2014-10-07	criteria provided, single submitter	clinical testing	The p.Arg230Trp variant in MYOZ2 has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/8600 of European American chr omosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS /; dbSNP rs372215131). Computational prediction tools and conservation analysi s do not provide strong support for or against an impact to the protein. Varia nts in MYOZ2 are associated with HCM (Osio 2007), though their role in other car diomyopathies remains unclear. In summary, the clinical significance of the Arg 230Trp variant is uncertain.
GeneDx	RCV000766492	SCV000250635	likely benign	not provided	2021-01-20	criteria provided, single submitter	clinical testing	Observed in a Chinese patient with type 1 LQTS and a family history of sudden death; this individual also harbored W176X and G589S compound heterozygous variants in the KCNQ1 gene, which authors felt were the likely cause of her disease (Lin et al., 2019); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 178092; Landrum 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: 31565860)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170138	SCV001332679	uncertain significance	Cardiomyopathy	2017-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001499991	SCV001704767	likely benign	Hypertrophic cardiomyopathy	2025-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362814	SCV002662929	likely benign	Cardiovascular phenotype	2020-11-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center	RCV000766492	SCV001922813	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000766492	SCV001929664	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000766492	SCV001980386	likely benign	not provided		no assertion criteria provided	clinical testing