Submissions for variant NM_033118.4(MYLK2):c.1584G>A (p.Arg528=)

gnomAD frequency: 0.00120  dbSNP: rs55807353

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154786	SCV000204466	likely benign	not specified	2015-07-28	criteria provided, single submitter	clinical testing	p.Arg528Arg in exon 12 of MYLK2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.1% (54/52690) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs55807353).
Invitae	RCV000471480	SCV000556770	benign	Hypertrophic cardiomyopathy 1	2024-01-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154786	SCV000699765	benign	not specified	2017-02-13	criteria provided, single submitter	clinical testing	Variant summary: The MYLK2 c.1584G>A (p.Arg528Arg)causes a synonymous change involving the alteration of a non-conserved nucleotide, 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding. However, these predictions have yet to be confirmed by functional studies. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 80/94662 (1/1183), which is approximately 34 times the estimated maximal expected allele frequency for a pathogenic MYLK2 variant of 1/40000, suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Therefore, the variant of interest has been classified as Benign.
GeneDx	RCV001529399	SCV001898321	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399344	SCV002705193	likely benign	Inborn genetic diseases	2022-05-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529399	SCV001742788	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529399	SCV001932472	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529399	SCV001971739	likely benign	not provided		no assertion criteria provided	clinical testing