Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068068 | SCV001233157 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 805 of the MYLK protein (p.Cys805Trp). This variant is present in population databases (rs372019566, gnomAD 0.002%). 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: 861522). 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 |
RCV001759842 | SCV002007435 | uncertain significance | not provided | 2022-11-07 | 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 supports that this missense variant has a deleterious effect on protein structure/function |
Ambry Genetics | RCV002445351 | SCV002733771 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-22 | criteria provided, single submitter | clinical testing | The p.C805W variant (also known as c.2415C>G), located in coding exon 14 of the MYLK gene, results from a C to G substitution at nucleotide position 2415. The cysteine at codon 805 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
Fulgent Genetics, |
RCV002480428 | SCV002777447 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-01 | criteria provided, single submitter | clinical testing |