Submissions for variant NM_002474.3(MYH11):c.3651+6_3651+11del

dbSNP: rs371843272

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182471	SCV000234816	benign	Familial thoracic aortic aneurysm and aortic dissection	2013-12-03	criteria provided, single submitter	clinical testing	The variant is found in TAAD panel(s).
Illumina Laboratory Services, Illumina	RCV000182471	SCV000395350	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473668	SCV000543724	benign	Aortic aneurysm, familial thoracic 4	2024-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000182471	SCV000903003	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-07-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000182471	SCV001333995	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-04-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003221840	SCV003917491	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	MYH11: BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689659	SCV005185821	uncertain significance	not specified	2024-05-15	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.3672+6_3672+11delGCTTTT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 1614204 control chromosomes (gnomAD database v4.0.0). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3672+6_3672+11delGCTTTT in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 201030). Based on the evidence outlined above, the variant was classified as uncertain significance.