ClinVar Miner

Submissions for variant NM_032578.3(MYPN):c.3263G>A (p.Arg1088His) (rs71584501)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000024483 SCV000577101 uncertain significance not provided 2017-04-11 criteria provided, single submitter clinical testing The R1088H variant of uncertain significance in the MYPN gene has been reported to segregate with DCM in four individuals from one family (Duboscq-Bidot et al., 2008). This 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). Although this substitution occurs at a position where amino acids with similar properties to arginine are tolerated across species, histidine is not tolerated at this position in any species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Immunolabelling of heart tissue from the proband with DCM harboring the R1088H variant showed decreased localization of MYPN at the Z-band area of left ventricular cardiac myofibrils; however, in vitro studies were unable to replicate this result as the cellular phenotype of R1088H protein was indistinguishable from wild type protein (Duboscq-Bidot et al., 2008). Additionally, the R1088H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Leiden Muscular Dystrophy (MYPN) RCV000024483 SCV000045787 not provided not provided 2012-04-27 no assertion provided curation
OMIM RCV000043540 SCV000071253 pathogenic Dilated cardiomyopathy 1KK 2008-01-01 no assertion criteria provided literature only

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