ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.3253A>G (p.Thr1085Ala) (rs75370906)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000223242 SCV000269298 benign not specified 2013-04-04 criteria provided, single submitter clinical testing Thr1085Ala in exon 18 of MYLK: This variant is not expected to have clinical sig nificance because it has been identified in 18.9% (832/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://; dbSNP rs75370906).
PreventionGenetics,PreventionGenetics RCV000223242 SCV000315285 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000617032 SCV000319508 benign Cardiovascular phenotype 2015-04-02 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 RCV000459681 SCV000440300 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 RCV000223242 SCV000528005 benign not specified 2016-09-28 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 RCV000459681 SCV000560671 benign Aortic aneurysm, familial thoracic 7 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000459681 SCV000884196 benign Aortic aneurysm, familial thoracic 7 2018-07-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000223242 SCV001361511 benign not specified 2019-08-26 criteria provided, single submitter clinical testing Variant summary: MYLK c.3253A>G (p.Thr1085Ala) 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 0.015 in 251472 control chromosomes in the gnomAD database, including 346 homozygotes. The observed variant frequency is approximately 606 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. A co-occurrence with a pathogenic variant has been reported (TGFBR1 c.1460G>A, p.Arg487Gln; LabCorp). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1x likely benign, 4x benign). Based on the evidence outlined above, the variant was classified as benign.

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