ClinVar Miner

Submissions for variant NM_032578.3(MYPN):c.3583G>A (p.Val1195Met) (rs71534280)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000024485 SCV000236067 uncertain significance not provided 2018-12-14 criteria provided, single submitter clinical testing The V1195M variant in the MYPN gene has been reported previously in one patient with sporadic DCM; however, additional clinical information was not provided (Duboscq-Bidot et al., 2008). This variant is observed in 53/24,012 alleles (0.22%) from individuals of African background, and 84/276,750 global alleles (0.03%) with no homozygous control individuals reported, in large population cohorts (Lek et al., 2016). The V1195M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Functional studies show that the V1195M variant results in disorganization of the sarcomere and decreased cell survival (Duboscq-Bidot et al., 2008). We interpret V1195M as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare 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 uncertain significance Cardiovascular phenotype 2017-10-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000024485 SCV000814868 likely benign not provided 2019-01-31 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
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

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