Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000472877 | SCV000550045 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1041 of the MYLK protein (p.Ala1041Thr). This variant is present in population databases (rs568590920, gnomAD 0.006%). This missense change has been observed in individual(s) with thoracic aortic aneurysm and/or dissection (PMID: 29907982). ClinVar contains an entry for this variant (Variation ID: 409711). 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 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. |
Fulgent Genetics, |
RCV002480415 | SCV000897058 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001552695 | SCV001773431 | uncertain significance | not provided | 2021-10-04 | criteria provided, single submitter | clinical testing | Has been reported in an individual with TAA, aortic root dilation, and bicuspid aortic valve (BAV) in published literature (Overwater et al., 2018); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 409711; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 29907982) |
Prevention |
RCV003418191 | SCV004108685 | uncertain significance | MYLK-related condition | 2023-08-01 | criteria provided, single submitter | clinical testing | The MYLK c.3121G>A variant is predicted to result in the amino acid substitution p.Ala1041Thr. This variant was reported as variant of unknown significance in an individual suspected of heritable thoracic aortic disorder (Table S1, Overwater et al. 2018. PubMed ID: 29907982). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-123419194-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |