Submissions for variant NM_016599.5(MYOZ2):c.-3dup

dbSNP: rs397517288

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039002	SCV000062680	benign	not specified	2013-02-25	criteria provided, single submitter	clinical testing	-3_-2insA in exon 2 of MYOZ2: This variant is not expected to have clinical sign ificance because it has been identified in 1.2% (51/4268) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/) . -3_-2insA in exon 2 of MYOZ2 (allele frequency = 1.2%, 51/4268) **
GeneDx	RCV000039002	SCV000250624	benign	not specified	2015-03-03	criteria provided, single submitter	clinical testing	This variant was found in CARDIOMYOPATHY,CRDMV2-PANCARD
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590300	SCV000699424	benign	not provided	2017-08-25	criteria provided, single submitter	clinical testing	Variant summary: The MYOZ2 c.-3dupA variant (also known as c.-3_-2insA) involves insertion of a nucleotide in non-coding exon 2. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may not affect binding of ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 176/115548 control chromosomes (1 homozygote) from ExAC, predominantly observed in the African subpopulation at a frequency of 0.015706 (157/9996). This frequency is about 628 times the estimated maximal expected allele frequency of a pathogenic MYOZ2 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories in ClinVar have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000619179	SCV000735727	benign	Cardiovascular phenotype	2018-02-13	criteria provided, single submitter	clinical testing	This alteration is classified as 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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625398	SCV000745236	benign	Hypertrophic cardiomyopathy 16	2015-09-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769183	SCV000900559	benign	Cardiomyopathy	2016-05-03	criteria provided, single submitter	clinical testing