ClinVar Genomic variation as it relates to human health
NM_000257.4(MYH7):c.1987C>T (p.Arg663Cys)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000257.4(MYH7):c.1987C>T (p.Arg663Cys)
Variation ID: 42874 Accession: VCV000042874.56
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 23426834 (GRCh38) [ NCBI UCSC ] 14: 23896043 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 7, 2015 May 1, 2024 Jan 29, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000257.4:c.1987C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000248.2:p.Arg663Cys missense NC_000014.9:g.23426834G>A NC_000014.8:g.23896043G>A NG_007884.1:g.13828C>T LRG_384:g.13828C>T LRG_384t1:c.1987C>T P12883:p.Arg663Cys - Protein change
- R663C
- Other names
- p.R663C:CGC>TGC
- Canonical SPDI
- NC_000014.9:23426833:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
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. |
|||
MYH7 | No evidence available | No evidence available |
GRCh38 GRCh37 |
3599 | 4856 |
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. |
---|---|---|---|---|
Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Oct 12, 2023 | RCV000158821.30 | |
Pathogenic (2) |
criteria provided, single submitter
|
Jul 3, 2019 | RCV000157358.11 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2024 | RCV000459608.18 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 1, 2021 | RCV000515169.4 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 9, 2021 | RCV000620403.4 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 15, 2023 | RCV001170504.7 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
MYH7-related skeletal myopathy
Myosin storage myopathy Hypertrophic cardiomyopathy 1 Myopathy, myosin storage, autosomal recessive Congenital myopathy 4A, autosomal dominant Myosin storage myopathy Dilated cardiomyopathy 1S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611215.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000546267.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 663 of the MYH7 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 663 of the MYH7 protein (p.Arg663Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (HCM) (PMID: 15358028, 15563892, 15858117, 18383048, 20800588, 22112859, 23233322, 23283745, 23690394). ClinVar contains an entry for this variant (Variation ID: 42874). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg663 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10750581, 11133230). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000736283.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
The p.R663C pathogenic mutation (also known as c.1987C>T), located in coding exon 16 of the MYH7 gene, results from a C to T substitution at … (more)
The p.R663C pathogenic mutation (also known as c.1987C>T), located in coding exon 16 of the MYH7 gene, results from a C to T substitution at nucleotide position 1987. The arginine at codon 663 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This alteration has been reported in numerous individuals with hypertrophic cardiomyopathy (HCM) from various ethnic groups (Van Driest SL et al, J. Am. Coll. Cardiol. 2004 Aug; 44(3):602-10; Yu B et al, J. Clin. Pathol. 2005 May; 58(5):479-85; Wang S et al, Clin Cardiol 2008 Mar; 31(3):114-8; Kassem HSh et al, J Cardiovasc Transl Res 2013 Feb; 6(1):65-80; Zhao Y et al. Int. J. Mol. Med., 2016 Jun;37:1511-20; Walsh R et al. Genet. Med., 2017 Feb;19:192-203; Jääskeläinen P et al. ESC Heart Fail, 2019 Apr;6:436-445). Additional alterations affecting the same amino acid, p.R663H (Gruver EJ et al, Am. J. Cardiol. 1999 Jun; 83(12A):13H-18H) and p.R663S (Richard P et al, Circulation 2003 May; 107(17):2227-32), were also reported in HCM patients, which may reflect a mutation hotspot at this position. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(Jul 03, 2019)
|
criteria provided, single submitter
Method: research
|
Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Klaassen Lab, Charite University Medicine Berlin
Accession: SCV000995885.1
First in ClinVar: Oct 19, 2019 Last updated: Oct 19, 2019 |
|
|
Pathogenic
(Jun 26, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059408.7
First in ClinVar: May 03, 2013 Last updated: Jul 03, 2020 |
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Number of individuals with the variant: 20
|
|
Pathogenic
(Oct 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000208756.17
First in ClinVar: Feb 24, 2015 Last updated: Nov 25, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21835320, 23690394, 27532257, 20800588, 30847666, 18383048, 23674513, 25714468, 25228707, 25351510, 23785128, 27247418, 15858117, 20350521, 23283745, 23233322, 25524337, 21799269, 15563892, 28606303, 27590665, 29497013, 29030401, 28193612, 29661763, 29743414, 27082122, 21310275, 22112859, 30775854, 32344918, 15358028, 32894683, 35653365, 35626289, 33673806, 32830170, 29300372) (less)
|
|
Pathogenic
(Jan 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175575.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The MYH7 c.1987C>T variant is classified as Pathogenic (PS4, PM1, PM2, PP1_Moderate, PP3.) The MYH7 c.1987C>T variant is a single nucleotide change in exon 18/40 … (more)
The MYH7 c.1987C>T variant is classified as Pathogenic (PS4, PM1, PM2, PP1_Moderate, PP3.) The MYH7 c.1987C>T variant is a single nucleotide change in exon 18/40 of the MYH7 gene, which is predicted to change the amino acid arginine at position 663 in the protein, to cysteine. This amino acid is within the conserved functional domain of the MYH7 protein where variation is expected to be disease causing (PM1). The variant has been reported in excess of 20 probands with a clinical presentation of Hypertrophic Cardiomyopathy (PMID#15358028, 33673806, 32344918, 30775854, 32894683, 35626289) (PS4) and is absent from population databases (PM2). This variant has been reported to segregate with disease (PMID #15563892, our cohort and SHaRE) (PP1_moderate). Computational predictions support a deleterious effect on the gene or gene product (PP3). The variant has been reported in dbSNP (rs397516127) is reported as disease causing in the HGMD database (CM973126) and is reported as pathogenic by multiple other diagnostic laboratories (ClinVar #42874). (less)
|
|
Pathogenic
(Apr 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002017670.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Mar 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333087.4
First in ClinVar: May 31, 2020 Last updated: Feb 04, 2024 |
|
|
Likely Pathogenic
(Oct 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004844789.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces arginine with cysteine at codon 663 in the myosin head/motor (S1) domain of the MYH7 protein. Computational prediction suggests that this … (more)
This missense variant replaces arginine with cysteine at codon 663 in the myosin head/motor (S1) domain of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant is found within a highly conserved region of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in more than 15 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, 15563892, 15858117, 18533079, 20350521, 23674513, 27532257, 31568572). A different variant occurring at the same codon, p.Arg663His, is a well documented pathogenic mutation (Clinvar variation ID: 42875), indicating that arginine at this position is important for MYH7 protein function. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Number of individuals with the variant: 1
|
|
Likely pathogenic
(Sep 06, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004356933.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with cysteine at codon 663 in the myosin head/motor (S1) domain of the MYH7 protein. Computational prediction suggests that this … (more)
This missense variant replaces arginine with cysteine at codon 663 in the myosin head/motor (S1) domain of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant is found within a highly conserved region of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in more than 15 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, 15563892, 15858117, 18533079, 20350521, 23674513, 27532257, 31568572). A different variant occurring at the same codon, p.Arg663His, is a well documented pathogenic mutation (Clinvar variation ID: 42875), indicating that arginine at this position is important for MYH7 protein function. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
|
|
Pathogenic
(Aug 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002585459.9
First in ClinVar: Oct 22, 2022 Last updated: Apr 15, 2024 |
Comment:
MYH7: PS4, PM2, PM5, PP2, PP3
Number of individuals with the variant: 1
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001919865.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Pathogenic
(Sep 17, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV000207096.2
First in ClinVar: Feb 07, 2015 Last updated: Apr 15, 2023 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Nov 04, 2016)
|
no assertion criteria provided
Method: provider interpretation
|
not provided
Affected status: unknown
Allele origin:
germline
|
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000924863.1
First in ClinVar: Jun 29, 2019 Last updated: Jun 29, 2019 |
Comment:
The following genes were evaluated for sequence changes and exonic deletions/duplications (ACTC1, ACTN2, BAG3, CAV3, CSRP3, DES, ELAC2, FHL1, GLA, LAMP2, MTO1, MYBPC3, MYH7, MYL2, … (more)
The following genes were evaluated for sequence changes and exonic deletions/duplications (ACTC1, ACTN2, BAG3, CAV3, CSRP3, DES, ELAC2, FHL1, GLA, LAMP2, MTO1, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR, VCL). The p.Arg663Cys (c.1987C>T) variant in the MYH7 gene was found. Given the strong case data, absence in controls, and presence of other pathogenic variants at the same codon, we classify this variant as very likely disease-causing (aka pathogenic). We feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). We re-reviewed the variant November 4th, 2016. This variant is present in ClinVar. It is classified as likely pathogenic by 3 labs (LMM, GeneDx and the CHEO) and pathogenic by Blueprint. Case Data: The Arg663Cys variant has been previously reported in at least 19 presumably unrelated individuals with HCM. It segregates with at least 4 affected relatives (SHaRe) and possibly an additional 7 (Song et al. 2005). Van Driest 2004: This variant was present in 1 out of 389 patients with HCM from their Mayo cohort. The variant was absent in 200 control individuals Song 2005: This variant was present in 1 out of 100 unrelated Chinese patients with HCM. There may be strong published segregation data, although the paper is a bit unclear about how to interpret this data: they found Arg663Cys in one proband, but in Table 3 they describe 8 affected individuals showing 100% penetrance of Arg663Cys. They do not specify that all 8 individuals are from one family; however, they do indicate that individuals with this variant have a family history of sudden cardiac death and that two other family members died of HCM at a young age. This variant was absent in 120 control individuals. This report is presumably redundant with Zou et al 2013. Of note, Zou et al report that the patient had an additional variant in MYH7, p.Gln892Lys (Q892K). The Q892K variant is not reported in the literature, has not been seen in gnomAD and is predicted to alter a splice site. Yu 2005: This variant was present in 2 out of 150 unrelated Australian patients with HCM. The variant was absent in 100 ethnically-matched controls. Olivotto 2008: This variant was present in 1 out of 61 patients with HCM for their Florence cohort. This patient was a 45-year old male with a maximum LV wall thickness of 27mm. This variant was absent from 150 adult ethnically-matched controls. This may be redundant with the report by Coppini et al since both include patients from the Florence cohort. Hirota 2010: This variant was present in at least 1 out of 93 probands with HCM. It is unclear how many probands had this variant. Witjas-Paalberends 2013: This variant was present in 1 out of 43 probands with HCM. It is unclear where these patients were recruited from, however it is possible there is overlap with Mook et al 2013 as both studies have multiple authors from Amsterdam. Mook 2013: This variant was found in a patient with HCM from a clinical genetic testing cohort in amsterdam. Kassem 2013: This variant was found in 1 of 199 unrelated HCM patients from Egypt. The variant was not present in 100 healthy controls. Zhao et al 2016: This variant was found in 1 out of 8 patients with HCM from their Chinese cohort. This variant was absent from 100 control subjects. Based on authors and institutions this appears to be a distinct case from Song et al and Zou et al. In the SHaRe consortium the variant has been seen in the following unrelated HCM patients: three from the Yale cohort, three from the Michigan cohort, five from Florence, and one from Brigham and Women’s. Some of these cases overlap with Coppini et al, Olivotto et al, and the cases from the genetic testing laboratories. If we do not count laboratory data, then we can take 11 unique cases from the SHaRe dataset. There are also four affected relatives from various SHaRe sites who carry the variant. Other variants have been reported at this same codon: p.Arg663His (we and others consider pathogenic) and p.Arg663Ser (not reviewed by us, likely pathogenic by one submitter in ClinVar). Van Driest et al (2004) described codon 663 as a ‘hotspot’ with 9 out of 58 (15%) patients with MYH7 variants in that study having a variant that involved codon 663. Induced pluripotent stem cells (iPSCs) harboring this variant, obtained from a ten-member family cohort with HCM, recapitulated many aspects of the HCM phenotype including cellular enlargement and contractile arrhythmia at the single-cell level (Lan et al 2013). This is a nonconservative amino acid change, resulting in the replacement of a positively-charged Arginine with a polar Cysteine capable of forming disulfide bridges. It is in the myosin head domain. This codon is enriched on the surface of the post-stroke motor domain, which is enriched for variation in patients with HCM. This indicates that this region in the myosin protein may be intolerant to genetic variation. Arginine at this location is highly conserved across vertebrate species (it is a Lysine in 2 species of bird). The adjacent residues are also highly conserved. In addition to variants at this residue (Arg663His, Arg663Ser), variation at nearby residues has also been associated with HCM, which supports the functional importance of this region of the protein: Arg652Gly, Leu658Val, Met659Ile, Met659Thr, Thr660Asn, His668Asn, Arg671Cys (HGMD professional version as of January 17, 2014). In silico analysis indicates that it is damaging to protein structure/function, according to GeneDx. LMM’s cardiomyopathy-specific algorithm agrees, according to ClinVar (Jordan et al, 2011). In total, the variant has not been seen in ~61,000 individuals from published control sets and databases approximating the general population. GeneDx reports that this variant is absent in at least 970 control individuals of various ethnic backgrounds in published control studies (Kassem et al., 2013; Mook et al 2013; Olivotto et al 2008; Song et al., 2005; Van Driest et al., 2004; Yu et al 2005- 100; Zhao et al 2016; Zou et al., 2013). This location is not well-covered in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/). However, it is well-covered Exome Aggregation Consortium Dataset (ExAC; http://exac.broadinstitute.org). This variant is absent in this dataset. This database currently includes variant calls on 60,706 unrelated individuals of African, Asian, European, Latino descent. The data includes 60,706 exomes (as of October 20, 2016). The average coverage at that site is more 65x. (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001739581.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001958736.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965231.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes. | Sepp R | Diagnostics (Basel, Switzerland) | 2022 | PMID: 35626289 |
Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients. | Hathaway J | BMC cardiovascular disorders | 2021 | PMID: 33673806 |
Clinical Utility of a Phenotype-Enhanced MYH7-Specific Variant Classification Framework in Hypertrophic Cardiomyopathy Genetic Testing. | Mattivi CL | Circulation. Genomic and precision medicine | 2020 | PMID: 32894683 |
Genetic Dissection of Hypertrophic Cardiomyopathy with Myocardial RNA-Seq. | Gao J | International journal of molecular sciences | 2020 | PMID: 32344918 |
Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3. | Kühnisch J | Clinical genetics | 2019 | PMID: 31568572 |
RIKADA Study Reveals Risk Factors in Pediatric Primary Cardiomyopathy. | Al-Wakeel-Marquard N | Journal of the American Heart Association | 2019 | PMID: 31333075 |
Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy. | Jääskeläinen P | ESC heart failure | 2019 | PMID: 30775854 |
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. | Walsh R | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27532257 |
Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system. | Zhao Y | International journal of molecular medicine | 2016 | PMID: 27082122 |
A systematic approach to the reporting of medically relevant findings from whole genome sequencing. | McLaughlin HM | BMC medical genetics | 2014 | PMID: 25714468 |
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 |
Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics. | Mook OR | Journal of medical genetics | 2013 | PMID: 23785128 |
Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy. | Valente AM | Circulation. Cardiovascular genetics | 2013 | PMID: 23690394 |
Mutations in MYH7 reduce the force generating capacity of sarcomeres in human familial hypertrophic cardiomyopathy. | Witjas-Paalberends ER | Cardiovascular research | 2013 | PMID: 23674513 |
Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. | Lan F | Cell stem cell | 2013 | PMID: 23290139 |
Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. | Zou Y | Molecular biology reports | 2013 | PMID: 23283745 |
Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program. | Kassem HSh | Journal of cardiovascular translational research | 2013 | PMID: 23233322 |
Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy. | Otsuka H | Circulation journal : official journal of the Japanese Circulation Society | 2012 | PMID: 22112859 |
Development of a high resolution melting method for the detection of genetic variations in hypertrophic cardiomyopathy. | Millat G | Clinica chimica acta; international journal of clinical chemistry | 2010 | PMID: 20800588 |
A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy. | Hirota T | Journal of cardiology | 2010 | PMID: 20350521 |
Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. | Olivotto I | Mayo Clinic proceedings | 2008 | PMID: 18533079 |
Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy. | Wang S | Clinical cardiology | 2008 | PMID: 18383048 |
Denaturing high performance liquid chromatography: high throughput mutation screening in familial hypertrophic cardiomyopathy and SNP genotyping in motor neurone disease. | Yu B | Journal of clinical pathology | 2005 | PMID: 15858117 |
Mutations profile in Chinese patients with hypertrophic cardiomyopathy. | Song L | Clinica chimica acta; international journal of clinical chemistry | 2005 | PMID: 15563892 |
Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. | Van Driest SL | Journal of the American College of Cardiology | 2004 | PMID: 15358028 |
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. | Richard P | Circulation | 2003 | PMID: 12707239 |
Beta-myosin heavy chain gene mutations and hypertrophic cardiomyopathy in Austrian children. | Greber-Platzer S | Journal of molecular and cellular cardiology | 2001 | PMID: 11133230 |
Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation. | Gruver EJ | The American journal of cardiology | 1999 | PMID: 10750581 |
click to load more click to collapse |
Text-mined citations for rs397516127 ...
HelpRecord last updated May 08, 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.