Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313411 | SCV000739267 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-06-23 | criteria provided, single submitter | clinical testing | The p.R954C variant (also known as c.2860C>T), located in coding exon 15 of the MYLK gene, results from a C to T substitution at nucleotide position 2860. The arginine at codon 954 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species, and cysteine is the reference amino acid in other vertebrate species. 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. |
| Invitae | RCV000688485 | SCV000816099 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-11-28 | 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 954 of the MYLK protein (p.Arg954Cys). This variant is present in population databases (rs749847711, gnomAD 0.006%). This missense change has been observed in individual(s) with Stanford type A aortic dissection (PMID: 34422331). This variant is also known as p.R885C. ClinVar contains an entry for this variant (Variation ID: 519968). 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 MYLK 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. |
| Fulgent Genetics, |
RCV002483733 | SCV002787941 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-08-19 | criteria provided, single submitter | clinical testing |