ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4345A>C (p.Lys1449Gln) (rs775809843)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000421159 SCV000535224 uncertain significance not provided 2016-12-21 criteria provided, single submitter clinical testing The c.948-10 T>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.948-10 T>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.948-10 T>G has no impact on splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000465853 SCV000543697 uncertain significance Aortic aneurysm, familial thoracic 4 2019-03-19 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 1456 of the MYH11 protein (p.Lys1456Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs775809843, ExAC 0.02%) but has not been reported in the literature in individuals with a MYH11-related disease. 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. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000771986 SCV000904941 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-06-17 criteria provided, single submitter clinical testing

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