Submissions for variant NM_002474.3(MYH11):c.1575+8del

dbSNP: rs769321167

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182492	SCV000234837	benign	Familial thoracic aortic aneurysm and aortic dissection	2013-12-26	criteria provided, single submitter	clinical testing	The variant is found in TAAD panel(s).
Invitae	RCV000234421	SCV000285776	likely benign	Aortic aneurysm, familial thoracic 4	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001375604	SCV001572511	benign	not specified	2021-04-08	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.1596+8delG alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00021 in 250854 control chromosomes. The observed variant frequency is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Thoracic Aortic Aneurysms And Dissections phenotype (1.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1596+8delG in individuals affected with Thoracic Aortic Aneurysms And Dissections 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 likely benign. Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000182492	SCV002042920	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2020-12-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002503708	SCV002796730	likely benign	Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	2021-12-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955107	SCV004774679	likely benign	MYH11-related condition	2021-07-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001729434	SCV001978115	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729434	SCV001980052	likely benign	not provided		no assertion criteria provided	clinical testing