Submissions for variant NM_032578.4(MYPN):c.1130G>A (p.Arg377Gln)

gnomAD frequency: 0.00058  dbSNP: rs147596628

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172071	SCV000054738	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000172071	SCV000236052	likely benign	not provided	2021-05-12	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar (ClinVar Variant ID# 191749; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 23861362, 28050010)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000183583	SCV000272181	uncertain significance	not specified	2015-04-09	criteria provided, single submitter	clinical testing	The p.Arg377Gln variant in MYPN has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.1% (13/11570) of Latino chromo somes and 43/66674 European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs147596628). Computational prediction tools and conservation analysis suggest that this variant may not impact the pro tein, though this information is not predictive enough to rule out pathogenicity . This variant is located in the last base of the exon, which is part of the 5' splice region. Computational tools do suggest an impact to splicing; however, th is information is not predictive enough to determine pathogenicity. In summary, in the presence of conflicting data, the clinical significance of the p.Arg377Gl n variant is uncertain.
Invitae	RCV000230164	SCV000291107	likely benign	Dilated cardiomyopathy 1KK	2024-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000244511	SCV000318391	likely benign	Cardiovascular phenotype	2019-03-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000230164	SCV000743679	uncertain significance	Dilated cardiomyopathy 1KK	2015-12-11	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852609	SCV000995312	likely benign	Cardiomyopathy	2019-01-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172071	SCV002497035	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MYPN: BP4
Mayo Clinic Laboratories, Mayo Clinic	RCV000172071	SCV002541072	uncertain significance	not provided	2021-04-30	criteria provided, single submitter	clinical testing