Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000536683 | SCV000650525 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 802 of the MYLK protein (p.Glu802Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 471710). 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. 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 |
RCV002060345 | SCV002496327 | uncertain significance | not provided | 2024-07-17 | 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 indicates that this missense variant does not alter protein structure/function |
| Fulgent Genetics, |
RCV002497169 | SCV002813350 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-10-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994013 | SCV004813333 | uncertain significance | not specified | 2024-02-12 | criteria provided, single submitter | clinical testing | Variant summary: MYLK c.2404G>A (p.Glu802Lys) results in a conservative amino acid change located in the Immunoglobulin subtype (IPR003599) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251458 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2404G>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 471710). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV004639273 | SCV005143188 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-04 | criteria provided, single submitter | clinical testing | The p.E802K variant (also known as c.2404G>A), located in coding exon 14 of the MYLK gene, results from a G to A substitution at nucleotide position 2404. The glutamic acid at codon 802 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |