Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002313450 | SCV000739333 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-06-06 | criteria provided, single submitter | clinical testing | The p.G54E variant (also known as c.161G>A), located in coding exon 1 of the MYLK gene, results from a G to A substitution at nucleotide position 161. The glycine at codon 54 is replaced by glutamic acid, an amino acid with some similar properties, and is located in the Ig-like C2-type 1 domain. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV001577928 | SCV001805423 | uncertain significance | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002499007 | SCV002790392 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003640928 | SCV004525472 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 54 of the MYLK protein (p.Gly54Glu). This variant is present in population databases (rs767453947, 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: 520009). 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 95%. 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. |