Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000024512 | SCV000236066 | benign | not provided | 2021-02-03 | criteria provided, single submitter | clinical testing | Identified in a patient with HCM in the published literature (Purevjav et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23299917, 22286171, 27535533) |
Soonchunhyang University Bucheon Hospital, |
RCV000206974 | SCV000267413 | uncertain significance | Dilated cardiomyopathy 1KK | 2016-03-18 | criteria provided, single submitter | reference population | |
Laboratory for Molecular Medicine, |
RCV000216191 | SCV000269405 | benign | not specified | 2015-06-03 | criteria provided, single submitter | clinical testing | p.Leu1161Ile in exon 18 of MYPN: This variant is not expected to have clinical s ignificance because it has been identified in 2.8% (320/11566) of Latino chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs138313730). |
Invitae | RCV000206974 | SCV000291122 | benign | Dilated cardiomyopathy 1KK | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000247848 | SCV000318077 | benign | Cardiovascular phenotype | 2016-04-25 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Center for Pediatric Genomic Medicine, |
RCV000024512 | SCV000511278 | likely benign | not provided | 2017-02-07 | criteria provided, single submitter | clinical testing | Converted during submission to Likely benign. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000624690 | SCV000740629 | uncertain significance | Primary familial dilated cardiomyopathy | 2017-03-28 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000206974 | SCV000743691 | likely benign | Dilated cardiomyopathy 1KK | 2017-07-28 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000206974 | SCV000745068 | benign | Dilated cardiomyopathy 1KK | 2017-05-31 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852614 | SCV000995317 | likely benign | Primary dilated cardiomyopathy; Cardiomyopathy; Heart failure | 2019-01-24 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000024512 | SCV001159431 | benign | not provided | 2020-08-11 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV000206974 | SCV001435224 | benign | Dilated cardiomyopathy 1KK | criteria provided, single submitter | research | The heterozygous p.Leu1161Ile variant in MYPN has been identified in an American Indian Alaskan individual with hypertrophic cardiomyopathy (PMID: 22286171). This variant has also been identified in >2% of Latino chromosomes and 5 homozygotes by ExAC (http://gnomad.broadinstitute.org/), and in 3 individuals from the NHLBI GO Exome Sequencing Project (PMID: 23299917). In summary, this variant meets criteria to be classified as benign for hypertrophic cardiomyopathy. | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000216191 | SCV004029750 | likely benign | not specified | 2023-07-29 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000024512 | SCV004042487 | benign | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | MYPN: BS1, BS2 |
Leiden Muscular Dystrophy |
RCV000024512 | SCV000045816 | not provided | not provided | 2012-04-27 | no assertion provided | curation | |
Clin |
RCV000206974 | SCV000244008 | uncertain significance | Dilated cardiomyopathy 1KK | 2013-06-27 | no assertion criteria provided | literature only | |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000024512 | SCV000280393 | benign | not provided | 2016-10-13 | no assertion criteria provided | provider interpretation | p.Leu1161Ile (c.3481 C>A) in the MYPN gene Given the weak disease-gene association, the weak case data, and the presence in ancestry-matched general population samples, we consider this variant a variant of uncertain significance. MYPN (NM_032578.2) encodes myopalladin, a protein component of the sarcomere. Heterozygous mutations in MYPN have been reported in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM) (Purevjav et al. 2012 Hum Molec Genet 21(9):2039-2053; Meyer et al. 2012 Eur J Hum Genet Epub ahead of print). However, when Megan Grove from our team reviewed the supporting data in 2012 we felt that it was weak. The variant has been seen in at least 1 unrelated case of hypertrophic cardiomyopathy (not including this patient's family). There is no segregation data available. Purevjav et al (2012) observed the variant in an American Indian/Alaskan male with HCM who had undergone myectomy. In silico analysis with PolyPhen-2 predicts the variant to be damaging. The variant occurs in the alpha-actinin binding domain. This is a conservative amino acid change from nonpolar leucine to a nonpolar isoleucine at a residue that is highly conserved across vertebrate species (it is a nonpolar phenylalanine in squirrel). It is predicted to be "probably damaging" and "tolerated" by PolyPhen and SIFT in silico analyses, respectively. [UPDATED in 2016] In total the variant has not been seen in at least 400 of >60,000 published controls and individuals from publicly available population datasets. It is present in 400 individuals in ExAC, across multiple ethnicities. The variant was reported in 3 of 4300 Caucasian individuals and 0 of 2203 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of September 12th, 2014). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. Note that other variants with strong evidence for pathogenicity have been seen at similar frequencies in this dataset so this does not necessarily rule out pathogenicity (Pan et al 2012). Per GeneDx, the variant was observed in the 1000 Genomes samples: 3/551 (0.5%) alleles from individuals of Asian background and in 1/349 (0.3%) alleles of individuals of Hispanic ancestry. The variant was not observed in the following published control samples: 1020 (Purejeav et al 2012). |
Clinical Genetics, |
RCV000216191 | SCV001919358 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000024512 | SCV001958066 | likely benign | not provided | no assertion criteria provided | clinical testing |