ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.4289-10dup (rs41431347)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000221432 SCV000269306 benign not specified 2015-06-09 criteria provided, single submitter clinical testing c.4289-3_4289-2insC in intron 24 of MYLK: This variant is not expected to have c linical significance it has been identified in 5% (3279/66076) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs200371896, rs41431347).
PreventionGenetics,PreventionGenetics RCV000221432 SCV000315299 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000340938 SCV000440282 likely benign Familial thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000474209 SCV000560667 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000221432 SCV000569605 benign not specified 2016-09-29 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000474209 SCV000604374 benign Aortic aneurysm, familial thoracic 7 2018-07-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620342 SCV000738323 benign Cardiovascular phenotype 2015-06-30 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Integrated Genetics/Laboratory Corporation of America RCV000221432 SCV001361510 benign not specified 2019-08-26 criteria provided, single submitter clinical testing Variant summary: MYLK c.4289-3dupC alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.035 in 248442 control chromosomes in the gnomAD database, including 170 homozygotes. The observed variant frequency is approximately 1404 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Aortopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4289-3dupC in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.