Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000689687 | SCV000817350 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2024-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1655 of the MYH11 protein (p.Arg1655Cys). This variant is present in population databases (rs369409348, gnomAD 0.009%). This missense change has been observed in individual(s) with thoracic aortic aneurysm or dissection (PMID: 22001912). ClinVar contains an entry for this variant (Variation ID: 161318). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYH11 protein function with a negative predictive value of 80%. 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. |
| Color Diagnostics, |
RCV001804858 | SCV002052661 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 1655 of the MYH11 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with thoracic aortic aneurysm and dissection (PMID: 22001912) and in an individual affected with ischemic stroke (PMID: 36973604). This variant has been identified in 6/251224 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. |
| Fulgent Genetics, |
RCV002478413 | SCV002797561 | uncertain significance | Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 | 2021-08-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001804858 | SCV005139083 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-03 | criteria provided, single submitter | clinical testing | The p.R1648C variant (also known as c.4942C>T), located in coding exon 33 of the MYH11 gene, results from a C to T substitution at nucleotide position 4942. The arginine at codon 1648 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant (referred to as NM_001040113.1:c.4963C>T, p.R1655C) has been detected in an individual with thoracic and abdominal aortic aneurysm/dissection (Sakai H et al. Hum Genet, 2012 Apr;131:591-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| CSER _CC_NCGL, |
RCV000148693 | SCV000190420 | uncertain significance | Aortic aneurysm | 2014-06-01 | no assertion criteria provided | research |