Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000818233 | SCV000958834 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2024-11-13 | 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 921 of the MYLK protein (p.Glu921Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 660931). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Ambry Genetics | RCV002433998 | SCV002752201 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-05 | criteria provided, single submitter | clinical testing | The p.E921K variant (also known as c.2761G>A), located in coding exon 15 of the MYLK gene, results from a G to A substitution at nucleotide position 2761. The glutamic acid at codon 921 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Fulgent Genetics, |
RCV002495165 | SCV002783245 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV003736913 | SCV004562714 | uncertain significance | not provided | 2023-10-19 | criteria provided, single submitter | clinical testing | The MYLK c.2761G>A; p.Glu921Lys variant (rs202223681), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 660931). This variant is found in the general population with an overall allele frequency of 0.01% (32/282,838 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.32). Due to limited information, the clinical significance of this variant is uncertain at this time. |