ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4127C>T (p.Ser1376Leu)

gnomAD frequency: 0.00008  dbSNP: rs553877450
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000792024 SCV000931296 uncertain significance Aortic aneurysm, familial thoracic 4 2023-06-25 criteria provided, single submitter clinical testing 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: 639271). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. This variant is present in population databases (rs553877450, gnomAD 0.04%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1383 of the MYH11 protein (p.Ser1383Leu).
Color Diagnostics, LLC DBA Color Health RCV001182047 SCV001347370 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-23 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 1383 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 10/281274 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 RCV001592968 SCV001817339 uncertain significance not provided 2019-06-07 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 that this variant does not alter protein structure/function
Ambry Genetics RCV001182047 SCV002632687 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-21 criteria provided, single submitter clinical testing The p.S1376L variant (also known as c.4127C>T), located in coding exon 30 of the MYH11 gene, results from a C to T substitution at nucleotide position 4127. The serine at codon 1376 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002487638 SCV002787685 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 2021-10-31 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.