Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000183582 | SCV000236051 | uncertain significance | not provided | 2017-02-02 | criteria provided, single submitter | clinical testing | This variant is denoted p.Asp369Asn (GAC>AAC): c.1105 G>A in exon 4 in the MYPN gene (NM_032578.3). The D369N variant in the MYPN gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D369N variant was not observed in approximately 6,500 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 D369N variant is a semi-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D369N as a variant of unknown significance. The variant is found in CARDIOMYOPATHY panel(s). |
| Labcorp Genetics |
RCV000524945 | SCV000659175 | uncertain significance | Dilated cardiomyopathy 1KK | 2022-11-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 201883). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. This variant is present in population databases (rs764775347, gnomAD 0.009%), including at least one homozygous and/or hemizygous individual. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 369 of the MYPN protein (p.Asp369Asn). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
| Center of Genomic medicine, |
RCV000857226 | SCV000999812 | uncertain significance | Hypertrophic cardiomyopathy | 2019-02-20 | criteria provided, single submitter | clinical testing | This variant was identified in a patient with familial hypertrophic cardiomyopathy, in combination with one variant in MYH7 and one variant in VCL |
| Ambry Genetics | RCV003380509 | SCV004088546 | uncertain significance | Cardiovascular phenotype | 2023-06-22 | criteria provided, single submitter | clinical testing | The p.D369N variant (also known as c.1105G>A), located in coding exon 3 of the MYPN gene, results from a G to A substitution at nucleotide position 1105. The aspartic acid at codon 369 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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. |