ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.383C>T (p.Ala128Val) (rs143896146)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228521 SCV000291198 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000242114 SCV000315293 benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000242114 SCV000332791 benign not specified 2015-07-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000228521 SCV000440347 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.
GeneDx RCV000242114 SCV000532241 benign not specified 2016-10-11 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000228521 SCV000604395 benign Aortic aneurysm, familial thoracic 7 2018-08-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000242114 SCV000711378 benign not specified 2013-04-04 criteria provided, single submitter clinical testing Ala128Val in exon 6 of MYLK: This variant is not expected to have clinical signi ficance because it has been identified in 12.9% (17/132) of Mexican chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov /projects/SNP; dbSNP rs143896146).
Ambry Genetics RCV000620257 SCV000738348 benign Cardiovascular phenotype 2015-05-22 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
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170678 SCV001333272 benign Familial thoracic aortic aneurysm and aortic dissection 2018-05-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000242114 SCV001362529 benign not specified 2019-11-18 criteria provided, single submitter clinical testing Variant summary: MYLK c.383C>T (p.Ala128Val) 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 0.016 in 282808 control chromosomes, predominantly at a frequency of 0.12 within the Latino subpopulation in the gnomAD database, including 286 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database greatly exceeds 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 Latino origin. To our knowledge, no occurrence of c.383C>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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