ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.5477C>T (p.Ala1826Val) (rs147187907)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618774 SCV000739274 uncertain significance Cardiovascular phenotype 2017-10-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238608 SCV000297361 uncertain significance Thoracic aortic aneurysm and aortic dissection 2015-12-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000657149 SCV000706616 uncertain significance not provided 2017-03-07 criteria provided, single submitter clinical testing
GeneDx RCV000657149 SCV000618223 uncertain significance not provided 2019-01-15 criteria provided, single submitter clinical testing Although the A1826V variant of uncertain significance in the MYLK gene has not been published as pathogenic or been reported as benign to our knowledge, it has been identified in conjunction with additional cardiogenetic variants in other individuals referred for connective tissue disorder genetic testing at GeneDx; however, thus far, segregation data is limited or absent due to the lack of clinical information provided and/or insufficient participation by informative family members. The A1826V variant is observed at a frequency of 53/126470 alleles (0.04%) in individuals of European (non-Finnish) background and in 10/30780 alleles (0.03%) in individuals of South Asian background in large population cohorts (Lek et al., 2016). The A1826V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.
Illumina Clinical Services Laboratory,Illumina RCV000238608 SCV000440268 uncertain significance Thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000557660 SCV000650564 uncertain significance Aortic aneurysm, familial thoracic 7 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1826 of the MYLK protein (p.Ala1826Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs147187907, ExAC 0.05%) but has not been reported in the literature in individuals with a MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 252775). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.