ClinVar Miner

Submissions for variant NM_032578.4(MYPN):c.3206G>A (p.Arg1069His)

gnomAD frequency: 0.00001  dbSNP: rs763362861
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183593 SCV000236062 uncertain significance not provided 2014-04-21 criteria provided, single submitter clinical testing This variant is denoted p.Arg1069His (CGC>CAC): c.3206 G>A in exon 16 of the MYPN gene (NM_032578.3). The R1069H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R1069H 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 R1069H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense mutations in nearby residues have been reported in association with cardiomyopathy, suggesting this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001852360 SCV002195484 uncertain significance Dilated cardiomyopathy 1KK 2022-06-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1069 of the MYPN protein (p.Arg1069His). This variant is present in population databases (rs763362861, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 201890). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV002492829 SCV002800109 uncertain significance Dilated cardiomyopathy 1KK; MYPN-related myopathy 2021-08-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV004020227 SCV003561203 uncertain significance Cardiovascular phenotype 2024-09-30 criteria provided, single submitter clinical testing The p.R1069H variant (also known as c.3206G>A), located in coding exon 15 of the MYPN gene, results from a G to A substitution at nucleotide position 3206. The arginine at codon 1069 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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