Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000441665 | SCV000536362 | uncertain significance | not provided | 2023-04-28 | criteria provided, single submitter | clinical testing | 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; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV000558787 | SCV000650518 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 670 of the MYLK protein (p.His670Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 393012). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYLK protein function. 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. |
| Ambry Genetics | RCV002418340 | SCV002720475 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-09-24 | criteria provided, single submitter | clinical testing | The p.H670L variant (also known as c.2009A>T), located in coding exon 12 of the MYLK gene, results from an A to T substitution at nucleotide position 2009. The histidine at codon 670 is replaced by leucine, an amino acid with similar 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. |