ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1724C>T (p.Pro575Leu) (rs761639849)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000472490 SCV000898845 uncertain significance Aortic aneurysm, familial thoracic 7 2018-11-30 criteria provided, single submitter clinical testing MYLK NM_053025.3 exon 13 p.Pro575Leu (c.1724C>T): This variant has not been reported in the literature but it is present in 0.01% (4/23476) of South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-123441055-G-A). This variant is present in ClinVar (Variation ID:409697). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000472490 SCV000550025 uncertain significance Aortic aneurysm, familial thoracic 7 2016-07-15 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 575 of the MYLK protein (p.Pro575Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs761639849, ExAC 0.01%) but has not been reported in the literature in individuals with a MYLK-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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