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

dbSNP: rs141564071

Total submissions: 8

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	RCV001711092	SCV000234833	benign	not provided	2018-06-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000245509	SCV000306201	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, 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 Diagnostics, LLC DBA Color Health	RCV000182488	SCV000910679	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-19	criteria provided, single submitter	clinical testing
Invitae	RCV000625181	SCV002404017	benign	Aortic aneurysm, familial thoracic 4	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625181	SCV000745977	benign	Aortic aneurysm, familial thoracic 4	2015-03-12	no assertion criteria provided	clinical testing