Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000648742 | SCV000770563 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2024-01-19 | 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 1301 of the MYLK protein (p.Arg1301Cys). This variant is present in population databases (rs368321325, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 539092). 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. |
| Gene |
RCV001592806 | SCV001814639 | uncertain significance | not provided | 2022-05-31 | 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 a deleterious effect |
| Molecular Genetics, |
RCV000648742 | SCV002503757 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2020-11-20 | criteria provided, single submitter | clinical testing | This sequence change is predicted to replace arginine with cysteine at codon 1301 of the MYLK protein (p.Arg1301Cys). The arginine residue is not conserved with cysteine present in multiple mammals (100 vertebrates, UCSC), and is located in the immunoglobulin I-set domain 8. There is a large physicochemical difference between arginine and cysteine. The variant is present in a large population cohort at a frequency of 0.006% (rs368321325, 16/282,670 alleles, 0 homozygotes in gnomAD v2.1), and has been reported as a variant of uncertain significance in ClinVar (ClinVar ID: 539092). Multiple lines of computational evidence have conflicting predictions for the missense substitution (4/6 algorithms predict benign). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as VARIANT OF UNCERTAIN SIGNIFICANCE . No criteria are met. |
| Ambry Genetics | RCV002358855 | SCV002620955 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-09-09 | criteria provided, single submitter | clinical testing | The p.R1301C variant (also known as c.3901C>T), located in coding exon 20 of the MYLK gene, results from a C to T substitution at nucleotide position 3901. The arginine at codon 1301 is replaced by cysteine, an amino acid with highly dissimilar properties. 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 alteration remains unclear. |
| Fulgent Genetics, |
RCV002493031 | SCV002780602 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-06 | criteria provided, single submitter | clinical testing |