Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311159 | SCV000320316 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-10-13 | criteria provided, single submitter | clinical testing | The p.G1639R variant (also known as c.4915G>C), located in coding exon 26 of the MYLK gene, results from a G to C substitution at nucleotide position 4915. The glycine at codon 1639 is replaced by arginine, an amino acid with 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. 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 variant remains unclear. |
| Invitae | RCV000685958 | SCV000813459 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2022-12-21 | 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 MYLK protein function. ClinVar contains an entry for this variant (Variation ID: 264399). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1639 of the MYLK protein (p.Gly1639Arg). |
| Fulgent Genetics, |
RCV002479988 | SCV002786838 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-10-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003153546 | SCV003842571 | uncertain significance | not provided | 2023-03-06 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |