Submissions for variant NM_032578.4(MYPN):c.1466G>A (p.Arg489Gln)

gnomAD frequency: 0.00006  dbSNP: rs141031460

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655029	SCV000776950	uncertain significance	Dilated cardiomyopathy 1KK	2023-12-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 489 of the MYPN protein (p.Arg489Gln). This variant is present in population databases (rs141031460, gnomAD 0.02%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 544030). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV002388157	SCV002698811	uncertain significance	Cardiovascular phenotype	2022-03-14	criteria provided, single submitter	clinical testing	The p.R489Q variant (also known as c.1466G>A), located in coding exon 7 of the MYPN gene, results from a G to A substitution at nucleotide position 1466. The arginine at codon 489 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is highly 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.
GeneDx	RCV000994419	SCV002762652	uncertain significance	not provided	2022-12-02	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a patient with DCM in published literature (van Lint et al., 2019); This variant is associated with the following publications: (PMID: 30847666)
Fulgent Genetics, Fulgent Genetics	RCV002485484	SCV002775667	uncertain significance	Dilated cardiomyopathy 1KK; MYPN-related myopathy	2021-12-23	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000994419	SCV004225254	uncertain significance	not provided	2022-08-16	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000994419	SCV001918909	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000994419	SCV001954071	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000994419	SCV001963364	uncertain significance	not provided		no assertion criteria provided	clinical testing