ClinVar Genomic variation as it relates to human health
NM_000256.3(MYBPC3):c.1321G>A (p.Glu441Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(12); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000256.3(MYBPC3):c.1321G>A (p.Glu441Lys)
Variation ID: 36601 Accession: VCV000036601.55
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p11.2 11: 47343051 (GRCh38) [ NCBI UCSC ] 11: 47364602 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2014 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000256.3:c.1321G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000247.2:p.Glu441Lys missense NC_000011.10:g.47343051C>T NC_000011.9:g.47364602C>T NG_007667.1:g.14652G>A LRG_386:g.14652G>A LRG_386t1:c.1321G>A LRG_386p1:p.Glu441Lys - Protein change
- E441K
- Other names
- p.E441K:GAG>AAG
- Canonical SPDI
- NC_000011.10:47343050:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00039
The Genome Aggregation Database (gnomAD), exomes 0.00014
1000 Genomes Project 30x 0.00016
Exome Aggregation Consortium (ExAC) 0.00016
The Genome Aggregation Database (gnomAD) 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00020
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MYBPC3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3679 | 3696 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (3) |
no assertion criteria provided
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Oct 2, 2015 | RCV000030279.6 | |
Uncertain significance (2) |
criteria provided, single submitter
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Apr 9, 2015 | RCV000035382.12 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV000603246.7 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Aug 31, 2022 | RCV000545018.8 | |
Uncertain significance (1) |
no assertion criteria provided
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Jul 14, 2017 | RCV000656154.2 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Mar 1, 2024 | RCV000656916.28 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 29, 2021 | RCV000618738.4 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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May 16, 2023 | RCV001175840.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 23, 2018 | RCV001105138.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 11, 2019 | RCV001256763.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000740239.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.E441K variant (also known as c.1321G>A), located in coding exon 15 of the MYBPC3 gene, results from a G to A substitution at nucleotide … (more)
The p.E441K variant (also known as c.1321G>A), located in coding exon 15 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 1321. The glutamic acid at codon 441 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in cohorts of individuals with hypertrophic cardiomyopathy; however, clinical details were limited in most reports, and some patients had co-occurring variants in other cardiac-related genes (Olivotto I et al. Mayo Clin. Proc., 2008 Jun;83:630-8; Marsiglia JD et al. Arq. Bras. Cardiol., 2010 Jan;94:10-7; Millat G et al. Eur J Med Genet Jul;53:261-7; Coto E et al. J Mol Diagn, 2012 Sep;14:518-24; Kassem HSh et al. J Cardiovasc Transl Res, 2013 Feb;6:65-80; Coppini R et al. J. Am. Coll. Cardiol., 2014 Dec;64:2589-600; Gajendrarao P et al. J Cardiovasc Transl Res, 2015 Jun;8:232-43). Functional studies using zebrafish models suggested this alteration may have an impact on the ventricular diastolic myocardial thickness; however, the clinical impact in the heterozygous state is uncertain (Da'as SI et al. Biochem. J., 2018 12;475:3933-3948). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
|
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Uncertain significance
(Jan 09, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003817152.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001148279.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
MYBPC3: BP4
Number of individuals with the variant: 5
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Uncertain significance
(Apr 09, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059030.5
First in ClinVar: May 03, 2013 Last updated: Oct 09, 2016 |
Comment:
The p.Glu441Lys variant in MYBPC3 has been observed in 10/62060 European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs193922377) and has been … (more)
The p.Glu441Lys variant in MYBPC3 has been observed in 10/62060 European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs193922377) and has been reported in at least 9 individuals with HCM, 2 o f whom carried other pathogenic variants (Olivotto 2008, Marsiglia 2010, Millat 2010, Olivotto 2011, Coto 2012, Kassem 2013). Our laboratory has identified this variant in 2 individuals with HCM and 1 individual with biatrial enlargement wh o carried another pathogenic HCM variant. The individual carrying the additional pathogenic HCM variant appeared to have an earlier onset of disease and a more severe presentation relative to the other patients carrying the Glu441Lys varian t. Computational prediction tools and conservation analysis do not provide stro ng support for or against an impact to the protein. In summary, the clinical sig nificance of the p.Glu441Lys variant is uncertain. The available data raise the possibility that it is independently disease causing but milder in isolation but additional data is needed to confirm its significance. (less)
Number of individuals with the variant: 5
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Uncertain significance
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 4
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138305.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Nov 26, 2018)
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criteria provided, single submitter
Method: research
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
Accession: SCV001245088.1
First in ClinVar: May 04, 2020 Last updated: May 04, 2020 |
Comment:
The MYBPC3 Glu441Lys variant has been identified in multiple HCM probands, including several compound heterozygotes (Liu X, et al., 2015; Olivotto I, et al., 2008; … (more)
The MYBPC3 Glu441Lys variant has been identified in multiple HCM probands, including several compound heterozygotes (Liu X, et al., 2015; Olivotto I, et al., 2008; Marsiglia JD, et al., 2010; Millat G, et al., 2010; Coto E, et al., 2012; Kassem HSh, et al., 2013, www.cardiodb.org/acgv/). We have identified this variant in 3 probands who were diagnosed at a young age (<18yo) and have severe hypertrophy, with maximum IVS measurements >30mm. All 3 probands also carry a second MYBPC3 variant, and one of these probands also carries a third variant in TNNT2. In one family MYBPC3 Glu441Lys did not segregate to another affected family member. The variant is present in the large Exome Aggregation Consortium dataset at an allele frequency of 0.00016 (http://exac.broadinstitute.org/), which is higher then expected for HCM. In silico tools SIFT, Polyphen2 and MutationTaster predict this variant to be deleterious. In summary, based on the adapted ACMG guidelines (Kelly MA, et al., 2018), the variant does not meet criteria for rarity (PM2) and as a result the identification of the variant in affected probands cannot be used, because only PP3 criteria are met, we classify MYBPC3 Glu441Lys as a variant of "uncertain significance" and suspect the variant may act as a modifier. (less)
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Uncertain significance
(Jul 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001262061.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Jul 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Left ventricular noncompaction 10
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001262060.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Sep 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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Arrhythmogenic right ventricular dysplasia 1
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433202.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
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Uncertain significance
(Aug 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000623524.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 441 of the MYBPC3 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 441 of the MYBPC3 protein (p.Glu441Lys). This variant is present in population databases (rs193922377, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with hypertrophic or dilated cardiomyopathy (PMID: 18533079, 20414521, 20624503, 21835320, 22765922, 23233322, 24093860, 26090888, 28420666, 30645170, 30731207, 30871747). ClinVar contains an entry for this variant (Variation ID: 36601). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MYBPC3 function (PMID: 30446606). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(May 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000208011.17
First in ClinVar: Feb 24, 2015 Last updated: Jun 03, 2023 |
Comment:
Identified in patients with cardiomyopathy referred for genetic testing at GeneDx and in published literature (Olivotto et al., 2008; Di Donna et al., 2010; Marsiglia … (more)
Identified in patients with cardiomyopathy referred for genetic testing at GeneDx and in published literature (Olivotto et al., 2008; Di Donna et al., 2010; Marsiglia et al., 2010; Millat et al., 2010; Coto et al., 2012, Kassem et al., 2013; Liu et al., 2015; Sousa et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25971843, 20173211, 33049255, 23233322, 23299917, 25637381, 22765922, 20624503, 26090888, 18533079, 27956910, 28518168, 21415409, 25524337, 27267291, 30645170, 30871747, 30731207, 30972196, 28420666, 30446606, 21835320, 20414521) (less)
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Uncertain significance
(May 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003837594.2
First in ClinVar: Mar 11, 2023 Last updated: Feb 04, 2024 |
|
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Uncertain significance
(Nov 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001339611.4
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glutamic acid with lysine at codon 441 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein … (more)
This missense variant replaces glutamic acid with lysine at codon 441 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 18533079, 20414521, 20624503, 21835320, 22765922, 23233322, 24093860, 26090888, 28420666, 30645170, 30972196, 32369506) or dilated cardiomyopathy (PMID: 30871747). However, some of these individuals also carried pathogenic variants in the same gene that could explain the observed phenotype (PMID: 18533079, 20624503, 32369506). In a study of two families, this variant has been observed in one affected individual but was absent in three other affected individuals (PMID: 30972196). This variant occurs at an appreciable frequency in the general population and has been identified in 41/278096 chromosomes by the Genome Aggregation Database (gnomAD). In summary, this variant has been observed in affected individuals, as well as in the general population. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Apr 11, 2014)
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no assertion criteria provided
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000207039.1
First in ClinVar: Feb 06, 2015 Last updated: Feb 06, 2015 |
Number of individuals with the variant: 1
|
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Uncertain significance
(Oct 02, 2015)
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no assertion criteria provided
Method: clinical testing
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Hypertrophic Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052946.2
First in ClinVar: Apr 04, 2013 Last updated: May 30, 2015 |
|
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Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922917.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Uncertain significance
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Cardiomyopathy, hypertrophic
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190406.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 |
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Uncertain significance
(May 03, 2013)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280210.1
First in ClinVar: Jun 01, 2016 Last updated: Jun 01, 2016 |
Comment:
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case … (more)
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. MYBPC3 p.Glu441Lys We consider this a variant of uncertain significance. This variant has been seen in at least 7 presumably unrelated individuals with hypertrophic cardiomyopathy (HCM). I was unable to find any reports of this variant with dilated cardiomyopathy. Notably, all of the individuals with this variant had at least one other sarcomere variant. There is no segregation data available on this variant. Olivotto et al. (2008) reported p.Glu441Lys in one patient with HCM who also carried another MYBPC3 variant (p.Glu258Lys). No data regarding phase or severity of phenotype were reported. Millat et al. (2010) reported one individual with HCM who had three variants on one MYBPC3 allele (p.Glu441Lys, p.Gln76Ter, p.Gly279Ala) and also had an additional variant in MYH7 (p.Ile1927Phe). Unfortunately age of onset and severity were not reported. Marsiglia et al (2010) reported the variant in one individual with HCM in Brazil (article is in Portuguese, further details not available). p.Glu441Lys has also been observed in two other unrelated individuals with HCM tested at GeneDx. One individual had two MYBPC3 missense variants and one MYH7 missense variant, was diagnosed with HCM in childhood and required transplant. The other individual was diagnosed with HCM as a child and was a compound heterozygote for this variant and an MYBPC3 frameshift variant (both parents were unaffected). The Seidmans' research group report this variant online in an individual who presumably has HCM and is a compound heterozygote for this variant and p.Glu258Lys (Merk et al 2005, http://genepath.med.harvard.edu/~seidman/cg3/muts/MYBPC3_Glu441Lys.html) This is a semi conservative amino acid substitution of a polar negative Glutamic Acid with a polar positive Lysine. Glutamic Acid is highly conserved at position 441. This variant was not identified in 150 presumably healthy individuals by Olivotto et al (2008). Millat et al (2010) did not do population studies. NHLBI Exome Sequence Variant Database reports p.Glu441Lys in 2 out of 4243 European American individuals and 3 out of 2138 African American individuals. The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. Based on these data, we consider this variant to be of uncertain significance. This classification is based on the fact that it has primarily (possibly only) been seen in combination with other variants and it has not yet been demonstrated that this variant can cause cardiomyopathy on its own or that it contributes in a significant way when in combination with other variants. (less)
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Uncertain significance
(Jul 14, 2017)
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no assertion criteria provided
Method: research
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Wolff-Parkinson-White pattern
Affected status: yes
Allele origin:
unknown
|
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Study: Candidate_variants_in_patients_with_ Wolff-Parkinson-White Syndrome
Accession: SCV000678348.1 First in ClinVar: Jun 02, 2018 Last updated: Jun 02, 2018 |
Comment:
This variant was identified in an individual with Wolff-Parkinson-White syndrome
Number of individuals with the variant: 1
|
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Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
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Hypertrophic cardiomyopathy 4
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733054.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958468.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy. | Nijenkamp LLAM | PloS one | 2020 | PMID: 32369506 |
Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug-induced arrhythmia and sudden unexplained deaths. | Martinez-Matilla M | Forensic science international. Genetics | 2019 | PMID: 31376648 |
A study of the pathogenicity of variants in familial heart disease. The value of cosegregation. | García-Molina E | American journal of translational research | 2019 | PMID: 30972196 |
Molecular characterization of Portuguese patients with dilated cardiomyopathy. | Sousa A | Revista portuguesa de cardiologia | 2019 | PMID: 30871747 |
Genetic Diagnostic Testing for Inherited Cardiomyopathies: Considerations for Offering Multi-Gene Tests in a Health Care Setting. | Daoud H | The Journal of molecular diagnostics : JMD | 2019 | PMID: 30731207 |
Key Value of RNA Analysis of MYBPC3 Splice-Site Variants in Hypertrophic Cardiomyopathy. | Singer ES | Circulation. Genomic and precision medicine | 2019 | PMID: 30645170 |
Hypertrophic cardiomyopathy-linked variants of cardiac myosin-binding protein C3 display altered molecular properties and actin interaction. | Da'as SI | The Biochemical journal | 2018 | PMID: 30446606 |
A multiplex PCR strategy to screen for known mutations in families with sudden cardiac death burden. | Duong G | Journal of biological methods | 2017 | PMID: 31453232 |
Using high-resolution variant frequencies to empower clinical genome interpretation. | Whiffin N | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28518168 |
Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy: Revisiting the Gene-Dose Effect. | Fourey D | Circulation. Cardiovascular genetics | 2017 | PMID: 28420666 |
Impact of disease-causing mutations on inter-domain interactions in cMyBP-C: a steered molecular dynamics study. | Krishnamoorthy N | Journal of biomolecular structure & dynamics | 2017 | PMID: 27267291 |
Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing. | Liu X | Scientific reports | 2015 | PMID: 26090888 |
Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations. | Coppini R | Journal of the American College of Cardiology | 2014 | PMID: 25524337 |
Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. | Marsiglia JD | American heart journal | 2013 | PMID: 24093860 |
New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. | Andreasen C | European journal of human genetics : EJHG | 2013 | PMID: 23299917 |
Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program. | Kassem HSh | Journal of cardiovascular translational research | 2013 | PMID: 23233322 |
Resequencing the whole MYH7 gene (including the intronic, promoter, and 3' UTR sequences) in hypertrophic cardiomyopathy. | Coto E | The Journal of molecular diagnostics : JMD | 2012 | PMID: 22765922 |
Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations. | Olivotto I | Journal of the American College of Cardiology | 2011 | PMID: 21835320 |
In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament. | Harris SP | Circulation research | 2011 | PMID: 21415409 |
Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. | Millat G | European journal of medical genetics | 2010 | PMID: 20624503 |
[Study of mutations causing hypertrophic cardiomyopathy in a group of patients from Espirito Santo, Brazil]. | Marsiglia JD | Arquivos brasileiros de cardiologia | 2010 | PMID: 20414521 |
Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. | Olivotto I | Mayo Clinic proceedings | 2008 | PMID: 18533079 |
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Text-mined citations for rs193922377 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.