Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172070 | SCV000051023 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Labcorp Genetics |
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. |
Gene |
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. |