Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313455 | SCV000739341 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-08-02 | criteria provided, single submitter | clinical testing | The p.A1160V variant (also known as c.3479C>T), located in coding exon 16 of the MYLK gene, results from a C to T substitution at nucleotide position 3479. The alanine at codon 1160 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. 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. |
| Invitae | RCV001860401 | SCV002206195 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2021-09-01 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 520014). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 1160 of the MYLK protein (p.Ala1160Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. |
| Gene |
RCV003320714 | SCV004025615 | uncertain significance | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |