ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.2533C>T (p.Arg845Cys) (rs3732485)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000211453 SCV000212179 likely benign Aortic aneurysm, familial thoracic 6 2015-03-11 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000222439 SCV000269292 benign not specified 2013-04-04 criteria provided, single submitter clinical testing Arg845Cys in exon 18 of MYLK: This variant is not expected to have clinical sign ificance because it has been identified in 1.4% (61/4402) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http://; dbSNP rs3732485).
PreventionGenetics,PreventionGenetics RCV000222439 SCV000315277 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000617024 SCV000319373 benign Cardiovascular phenotype 2015-01-23 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV000463249 SCV000440315 benign Aortic aneurysm, familial thoracic 7 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000463249 SCV000560677 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000463249 SCV000604380 benign Aortic aneurysm, familial thoracic 7 2018-08-19 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000243617 SCV000900712 benign Familial thoracic aortic aneurysm and aortic dissection 2016-02-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000222439 SCV001338204 benign not specified 2020-02-17 criteria provided, single submitter clinical testing Variant summary: MYLK c.2533C>T (p.Arg845Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.027 in 246212 control chromosomes in the gnomAD database, including 240 homozygotes. The observed variant frequency is approximately 1080-fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Aortopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2533C>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000222439 SCV000525669 benign not specified 2016-12-06 no assertion criteria provided 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.

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