ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.3749G>A (p.Arg1250His) (rs139817477)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508092 SCV000604390 uncertain significance not specified 2017-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621319 SCV000739304 uncertain significance Cardiovascular phenotype 2016-08-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238683 SCV000297358 uncertain significance Thoracic aortic aneurysm and aortic dissection 2015-10-30 criteria provided, single submitter clinical testing
Invitae RCV000466008 SCV000550038 uncertain significance Aortic aneurysm, familial thoracic 7 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1250 of the MYLK protein (p.Arg1250His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs139817477, ExAC 0.009%) but has not been reported in the literature in individuals with a MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 252772). 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. 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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