Submissions for variant NM_032578.4(MYPN):c.3583G>A (p.Val1195Met)

gnomAD frequency: 0.00083  dbSNP: rs71534280

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000024485	SCV000236067	likely benign	not provided	2020-05-28	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22892539, 22337857, 23299917, 18006477, 27896284)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000219549	SCV000272186	uncertain significance	not specified	2017-05-18	criteria provided, single submitter	clinical testing	The p.Val1195Met variant in MYPN has been reported in at least 2 individuals wit h DCM (Duboscq-Bidot 2008, LMM data). It has been reported in ClinVar (Variant I D: 31792) with conflicting interpretations. This variant has also been identifie d in 0.2% (53/24012) of African chromosomes by the Genome Aggregation Database ( gnomAD, http://gnomad.broadinstitute.org; dbSNP rs71534280). Computational predi ction tools and conservation analysis suggest that this variant may impact the p rotein, though this information is not predictive enough to determine pathogenic ity. A single in vitro functional study reports that the p.Val1195Met variant ma y impact protein function (Duboscq-Bidot 2008). However, these types of assays m ay not accurately represent biological function. In summary, the clinical signif icance of the p.Val1195Met variant is uncertain.
Ambry Genetics	RCV000621596	SCV000736229	likely benign	Cardiovascular phenotype	2019-04-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000043543	SCV000814868	likely benign	Dilated cardiomyopathy 1KK	2024-01-22	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000043543	SCV000930499	uncertain significance	Dilated cardiomyopathy 1KK	2019-04-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000219549	SCV004241220	likely benign	not specified	2023-12-17	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003989299	SCV004807274	uncertain significance	MYPN-related myopathy	2024-03-26	criteria provided, single submitter	clinical testing
Leiden Muscular Dystrophy (MYPN)	RCV000024485	SCV000045789	not provided	not provided	2012-04-27	no assertion provided	curation
OMIM	RCV000043543	SCV000071256	pathogenic	Dilated cardiomyopathy 1KK	2008-01-01	no assertion criteria provided	literature only
Clinical Genetics, Academic Medical Center	RCV000024485	SCV001917050	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000024485	SCV001926413	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004730857	SCV005338662	likely benign	MYPN-related disorder	2024-09-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).