ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5596G>A (p.Glu1866Lys)

gnomAD frequency: 0.00003  dbSNP: rs148743922
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247569 SCV000319368 uncertain significance Cardiovascular phenotype 2014-11-25 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
Invitae RCV000553332 SCV000641075 uncertain significance Aortic aneurysm, familial thoracic 4 2023-05-10 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYH11-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function. ClinVar contains an entry for this variant (Variation ID: 263884). This variant is present in population databases (rs148743922, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1873 of the MYH11 protein (p.Glu1873Lys).
Color Diagnostics, LLC DBA Color Health RCV000777865 SCV000913871 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-11-03 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1873 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 11/282646 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001753734 SCV002005181 uncertain significance not provided 2019-09-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 263884; Landrum et al., 2016)

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.