ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.2644G>A (p.Ala882Thr)

gnomAD frequency: 0.00003  dbSNP: rs199476411
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206957 SCV000659194 uncertain significance Dilated cardiomyopathy 1KK 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 882 of the MYPN protein (p.Ala882Thr). This variant is present in population databases (rs199476411, gnomAD 0.008%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 22286171). ClinVar contains an entry for this variant (Variation ID: 31821). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000619353 SCV000735458 uncertain significance Cardiovascular phenotype 2022-12-20 criteria provided, single submitter clinical testing The p.A882T variant (also known as c.2644G>A), located in coding exon 11 of the MYPN gene, results from a G to A substitution at nucleotide position 2644. The alanine at codon 882 is replaced by threonine, an amino acid with similar properties. This alteration co-occurred with a second MYPN variant and an MYH7 variant in a proband with dilated cardiomyopathy (DCM) whose sibling, also with DCM, had the same MYH7 variant as the proband and a different MYPN variant (Purevjav E et al. Hum Mol Genet. 2012;21:2039-53). This alteration was also detected in a sudden unexplained death cohort (Lin Y et al. Circ Cardiovasc Genet, 2017 Dec;10). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002482905 SCV002783987 uncertain significance Dilated cardiomyopathy 1KK; MYPN-related myopathy 2021-08-13 criteria provided, single submitter clinical testing
Leiden Muscular Dystrophy (MYPN) RCV000024514 SCV000045818 not provided not provided 2012-04-27 no assertion provided curation
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000206957 SCV000244015 uncertain significance Dilated cardiomyopathy 1KK 2013-06-27 no assertion criteria provided literature only

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