ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.755-12C>T (rs138877679)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000441344 SCV000532220 benign not specified 2017-12-20 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000441344 SCV000711379 likely benign not specified 2013-04-04 criteria provided, single submitter clinical testing c.755-12C>T in intron 8 of MYLK: This variant is not expected to have clinical significance because it does not cause the splice site sequence to diverge from consensus and it has been identified in 0.2% (183/121404) chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1388776 79).
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659936 SCV000781840 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001146464 SCV001307210 likely benign Aortic aneurysm, familial thoracic 7 2018-01-13 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000441344 SCV001362531 benign not specified 2019-12-16 criteria provided, single submitter clinical testing Variant summary: MYLK c.755-12C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.002 in 251476 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 79-folds over 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.755-12C>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions (evaluation after 2014) cite the variant once as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign.

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