ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5666C>T (p.Ala1889Val) (rs369950711)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182535 SCV000234883 uncertain significance not provided 2018-03-22 criteria provided, single submitter clinical testing p.Ala1889Val (GCA>GTA): c.5666 C>T in exon 40 of the MYH11 gene (NM_002474.2). The A1889V variant in the MYH11 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The A1889V variant is a conservative amino acid substitution as these residues share similar properties, and are least likely to impact secondary structure. The A1889 residue is conserved across species. The A1889V variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Nevertheless, no mutations in nearby residues have been reported in association with TAAD.With the clinical and molecular information available at this time, we cannot definitively determine if A1889V is a disease-causing mutation or a rare benign variant. This result cannot be interpreted for diagnosis or used for family member screening at this time. The variant is found in TAAD panel(s).
Ambry Genetics RCV000251036 SCV000318736 uncertain significance Cardiovascular phenotype 2017-03-03 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000771912 SCV000904678 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-02-11 criteria provided, single submitter clinical testing
Invitae RCV000814301 SCV000954704 uncertain significance Aortic aneurysm, familial thoracic 4 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1896 of the MYH11 protein (p.Ala1896Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs369950711, ExAC 0.009%). This variant has been observed in an individual referred for thoracic aortic aneurysm and dissection testing (PMID: 29510914). ClinVar contains an entry for this variant (Variation ID: 201090). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Illumina Clinical Services Laboratory,Illumina RCV000814301 SCV001279557 uncertain significance Aortic aneurysm, familial thoracic 4 2018-01-15 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000771912 SCV001333413 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-10-16 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000814301 SCV001428666 uncertain significance Aortic aneurysm, familial thoracic 4 2019-05-31 criteria provided, single submitter clinical testing

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.