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

dbSNP: rs41431347

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham 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, part of Exact Sciences	RCV000221432	SCV000315299	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, 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	2024-02-01	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.
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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001701799	SCV002058048	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701799	SCV001931152	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000221432	SCV001968388	benign	not specified		no assertion criteria provided	clinical testing