ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.662A>T (p.Asp221Val)

dbSNP: rs185841477
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172070 SCV000051023 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000225863 SCV000291126 uncertain significance Dilated cardiomyopathy 1KK 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 221 of the MYPN protein (p.Asp221Val). This variant is present in population databases (rs185841477, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with sudden unexpected death in infancy (SUDI) (PMID: 26350513). ClinVar contains an entry for this variant (Variation ID: 191748). 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. 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.
GeneDx RCV000172070 SCV001817686 likely benign not provided 2020-10-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28831623, 27662471, 26350513)
Ambry Genetics RCV002362881 SCV002661889 uncertain significance Cardiovascular phenotype 2022-09-29 criteria provided, single submitter clinical testing The p.D221V variant (also known as c.662A>T), located in coding exon 1 of the MYPN gene, results from an A to T substitution at nucleotide position 662. The aspartic acid at codon 221 is replaced by valine, an amino acid with highly dissimilar properties. This variant has been detected in individuals and cohorts with various phenotypes including coronary heart disease, ventricular arrhythmia, dilated cardiomyopathy, sudden unexplained death, and restrictive cardiomyopathy; however, details were limited and variants in other cardiac-related genes were detected in some cases (Kostareva A et al. PLoS One Sep;11:e0163362; Hertz CL et al. Eur J Hum Genet, 2016 06;24:817-22; Hertz CL et al. Eur J Hum Genet, 2016 06;24:817-22; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309; Kars ME et al. Proc Natl Acad Sci U S A, 2021 09;118; Guelly C et al. PeerJ, 2021 Jan;9:e10711). This variant has also been detected in an exome cohort; however, details were limited (Ng D et al. Circ Cardiovasc Genet. 2013 Aug;6(4):337-46). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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