Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049729 | SCV001213797 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2022-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 333 of the MYLK protein (p.Pro333Leu). This variant is present in population databases (rs568039936, gnomAD 0.04%). 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: 846429). 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. |
| Ambry Genetics | RCV002379541 | SCV002694053 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2022-02-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| CHEO Genetics Diagnostic Laboratory, |
RCV002379541 | SCV003837879 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003232192 | SCV003929673 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994197 | SCV004813334 | likely benign | not specified | 2024-02-05 | criteria provided, single submitter | clinical testing | Variant summary: MYLK c.998C>T (p.Pro333Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 248820 control chromosomes. The observed variant frequency is approximately 30.54 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Aortopathy phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.998C>T 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: 846429). Based on the evidence outlined above, the variant was classified as likely benign. |