ClinVar Miner

Submissions for variant MYH11:c.503-14_503-12del (rs141564071)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000245509 SCV000052969 benign not specified 2018-09-12 criteria provided, single submitter clinical testing Variant summary: MYH11 c.503-14_503-12delCTT alters a 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 0.011 in 276760 control chromosomes, predominantly at a frequency of 0.1 within the African subpopulation in the gnomAD database, including 121 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 79999.95 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.503-14_503-12delCTT in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three 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/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000245509 SCV000234833 benign not specified 2018-03-12 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.
PreventionGenetics,PreventionGenetics RCV000245509 SCV000306201 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000182488 SCV000395396 likely benign Familial thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000625181 SCV000744029 benign Aortic aneurysm, familial thoracic 4 2014-10-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000182488 SCV000910679 benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-19 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000625181 SCV000745977 benign Aortic aneurysm, familial thoracic 4 2015-03-12 no assertion criteria provided clinical testing

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