ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.479C>G (p.Pro160Arg) (rs111256888)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000253654 SCV000315307 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000248689 SCV000319371 benign Cardiovascular phenotype 2015-02-11 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
GeneDx RCV000253654 SCV000533277 benign not specified 2016-12-01 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 RCV001000299 SCV000560656 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769344 SCV000900727 likely benign Familial thoracic aortic aneurysm and aortic dissection 2017-09-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000299 SCV001156975 benign Aortic aneurysm, familial thoracic 7 2019-03-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000253654 SCV001361520 benign not specified 2019-10-15 criteria provided, single submitter clinical testing Variant summary: MYLK c.479C>G (p.Pro160Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 250756 control chromosomes, predominantly at a frequency of 0.016 within the African or African-American subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 640 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 a benign polymorphism found primarily in populations of African or African-American origin. c.479C>G has been reported in the literature without strong evidence of causality (Pal_2017). This report does not provide unequivocal conclusions about association of the variant with Aortopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign (x3) and likely benign (x1). Based on the evidence outlined above, the variant was classified as benign.

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