ClinVar Miner

Submissions for variant NM_033118.4(MYLK2):c.173C>A (p.Ala58Asp) (rs138130914)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172570 SCV000051017 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039784 SCV000063473 likely benign not specified 2015-02-18 criteria provided, single submitter clinical testing p.Ala58Asp in exon 3 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 0.9% (150/16508) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs138130914).
GeneDx RCV000039784 SCV000236020 likely benign not specified 2017-04-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001081175 SCV000291169 benign Familial hypertrophic cardiomyopathy 1 2020-12-08 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770567 SCV000902016 benign Cardiomyopathy 2018-06-28 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000770567 SCV000995695 likely benign Cardiomyopathy 2017-04-04 criteria provided, single submitter clinical testing
Genetics and Genomics Program,Sidra Medicine RCV001293152 SCV001434142 likely benign Hypertrophic cardiomyopathy criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039784 SCV001448539 benign not specified 2020-11-17 criteria provided, single submitter clinical testing Variant summary: MYLK2 c.173C>A (p.Ala58Asp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 250664 control chromosomes, predominantly at a frequency of 0.0097 within the South Asian subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 390 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK2 causing Hypertrophic Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.173C>A in individuals affected with Hypertrophic Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (2x) / likely benign (3x). Based on the evidence outlined above, the variant was classified as benign.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000039784 SCV000280391 uncertain significance not specified 2014-10-15 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease

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