ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4578+1G>A

dbSNP: rs397514037
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412872 SCV000491222 pathogenic not provided 2020-09-17 criteria provided, single submitter clinical testing Has been reported in one family with thoracic aortic aneurysm and dissection (TAAD) and patent ductus arteriosis (PDA) (Renard et al., 2013), and reported under alternative nomenclature (c.4599+1 G>A) in a Chinese proband (Yang et al., 2016); Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 372759; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to destroy the canonical splice donor site in intron 32 and is predicted to cause an in-frame deletion; This variant is associated with the following publications: (PMID: 32037394, 21937134, 27611364, 16444274)
Invitae RCV000550319 SCV000641043 pathogenic Aortic aneurysm, familial thoracic 4 2024-01-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 33 of the MYH11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH11 cause disease. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with autosomal dominant thoracic aortic aneurysm/dissection (PMID: 16444274, 21937134, 27611364). This variant is also known as IVS32+1G>A. ClinVar contains an entry for this variant (Variation ID: 372759). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003150197 SCV003838488 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2021-10-05 criteria provided, single submitter clinical testing

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