Submissions for variant NM_032578.4(MYPN):c.3934C>T (p.Arg1312Trp)

gnomAD frequency: 0.00012  dbSNP: rs142354704

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172082	SCV000051030	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000172082	SCV000604433	uncertain significance	not provided	2017-05-26	criteria provided, single submitter	clinical testing	The p.Arg1312Trp variant (rs142354704) has been previously observed in a single individual included in a large cohort of cardiomyopathy patients (Ng 2013) and is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 191760). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in East Asian populations of 0.25% (identified in 48 out of 18,870 chromosomes). The arginine at codon 1312 is moderately conserved considering 11 species (Alamut software v2.9), and computational analyses return mixed results regarding the effect of this variant on MYPN protein structure/function (SIFT: damaging, PolyPhen2: benign, and Mutation Taster: disease causing). Thus, based on the available information, the clinical significance of the p.Arg1312Trp variant cannot be determined with certainty.
Ambry Genetics	RCV000620740	SCV000735911	likely benign	Cardiovascular phenotype	2020-08-13	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.
Invitae	RCV001089060	SCV000816288	likely benign	Dilated cardiomyopathy 1KK	2024-01-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000172082	SCV001820862	likely benign	not provided	2020-01-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30847666, 23861362)
Revvity Omics, Revvity	RCV000172082	SCV003810992	uncertain significance	not provided	2020-12-28	criteria provided, single submitter	clinical testing
Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University	RCV003319183	SCV003932377	uncertain significance	Primary dilated cardiomyopathy	2023-06-01	criteria provided, single submitter	clinical testing