ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4604G>A (p.Arg1535Gln) (rs137934837)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417390 SCV000234868 likely benign not specified 2018-01-24 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.
Invitae RCV000755578 SCV000285794 likely benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617079 SCV000317804 likely benign Cardiovascular phenotype 2018-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Subpopulation frequency in support of benign classification
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000227161 SCV000493765 uncertain significance Aortic aneurysm, familial thoracic 4 2015-09-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755578 SCV000604354 likely benign not provided 2017-05-05 criteria provided, single submitter clinical testing The MYH11 c.4604G>A; p.Arg1535Gln variant (rs137934837), also known as c.4625G>A; p.Arg1542Gln, is reported in the literature in individuals with thoracic aortic aneurysm and dissection (Sakai 2012, Zarate 2016, Ziganshin 2015, Zhu 2007). However, the variant has been found to co-occur with other pathogenic variants in causative genes in the literature (Sakai 2012), and in patients tested at ARUP Laboratories. A case-control study also found the variant at equivalent frequencies in cases and controls (Zhu 2007). It is listed in ClinVar (Variation ID: 180418), and observed in the general population databases at a frequency of 0.14 percent in the 1000 Genomes Project (7/5008 alleles), 0.16 percent in the Exome Variant Server (21/12994 alleles), and 0.22 percent in the Genome Aggregation Database (599/277148 alleles, including 1 homozygote). The arginine at position 1535 is highly conserved, and computational analyses (PolyPhen-2, SIFT) predict that the variant is deleterious. However, given its occurrence in individuals with a pathogenic variant associated with their disorders, the variant is considered likely benign. References: Sakai H et al. Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods: resequencing microarray technology and next-generation sequencing. Hum Genet. 2012 Apr;131(4):591-9. Zarate YA et al. Aortic dilation, genetic testing, and associated diagnoses. Genet Med. 2016 Apr;18(4):356-63. Ziganshin BA et al. Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting. Ann Thorac Surg. 2015 Nov;100(5):1604-11. Zhu L et al. Investigation of the MYH11 gene in sporadic patients with an isolated persistently patent arterial duct. Cardiol Young. 2007 Dec;17(6):666-72.
Center for Human Genetics, Inc RCV000659922 SCV000781826 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Color RCV000157332 SCV000910817 likely benign Thoracic aortic aneurysm and aortic dissection 2018-03-05 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000157332 SCV000207069 uncertain significance Thoracic aortic aneurysm and aortic dissection 2014-05-19 no assertion criteria provided clinical testing

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