ClinVar Miner

Submissions for variant NM_032578.3(MYPN):c.2642A>T (p.Asn881Ile) (rs71584493)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000157383 SCV000207121 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-03-03 no assertion criteria provided clinical testing
GeneDx RCV000024503 SCV000589427 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing The N881I variant in the MYPN gene has not been reported previously as a pathogenic variant to our knowledge. N881I has been reported as a polymorphism, identified in a cohort of patients with dilated cardiomyopathy, as it was also observed in <1% of 400 control subjects (Duboscq-Bidot et al., 2008). However, the N881I variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N881I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N881I as a variant of uncertain significance.
Invitae RCV000698832 SCV000827521 uncertain significance Dilated cardiomyopathy 1KK 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 881 of the MYPN protein (p.Asn881Ile). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs71584493, ExAC 0.006%). This variant has not been reported in the literature in individuals with MYPN-related disease. ClinVar contains an entry for this variant (Variation ID: 31810). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Leiden Muscular Dystrophy (MYPN) RCV000024503 SCV000045807 not provided not provided 2012-04-27 no assertion provided curation

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