ClinVar Genomic variation as it relates to human health
NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr)
Variation ID: 42953 Accession: VCV000042953.59
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 23421008 (GRCh38) [ NCBI UCSC ] 14: 23890217 (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 Nov 15, 2015 Jun 17, 2024 Mar 22, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000257.4:c.3286G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000248.2:p.Asp1096Tyr missense NC_000014.9:g.23421008C>A NC_000014.8:g.23890217C>A NG_007884.1:g.19654G>T LRG_384:g.19654G>T LRG_384t1:c.3286G>T - Protein change
- D1096Y
- Other names
- NM_000257.3(MYH7):c.3286G>T
- Canonical SPDI
- NC_000014.9:23421007:C: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00011
The Genome Aggregation Database (gnomAD) 0.00013
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
The Genome Aggregation Database (gnomAD), exomes 0.00015
Exome Aggregation Consortium (ExAC) 0.00016
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 |
3604 | 4861 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Jul 30, 2015 | RCV000201875.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Jun 5, 2021 | RCV000620264.10 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
|
Mar 29, 2023 | RCV000656921.34 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
May 21, 2019 | RCV000491282.17 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 25, 2024 | RCV000529912.14 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Nov 3, 2022 | RCV000590886.10 | |
Likely benign (4) |
reviewed by expert panel
|
Mar 22, 2021 | RCV000758039.20 | |
Benign (1) |
criteria provided, single submitter
|
May 21, 2019 | RCV001114182.11 | |
See cases
|
Uncertain significance (1) |
criteria provided, single submitter
|
Nov 17, 2020 | RCV001265537.8 |
Uncertain significance (1) |
criteria provided, single submitter
|
May 21, 2019 | RCV003320065.8 | |
MYH7-related disorder
|
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 6, 2023 | RCV004534742.1 |
click to load more click to collapse |
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. |
|
---|---|---|---|---|---|
Likely benign
(Mar 22, 2021)
|
reviewed by expert panel
Method: curation
|
Cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Cardiomyopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000577981.6 First in ClinVar: Mar 08, 2017 Last updated: Sep 10, 2021 |
Comment:
The c.3286G>T (p.Asp1096Tyr) variant in MYH7 has been identified in 0.023% (FAF 95% CI; 40/129162) of European chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a … (more)
The c.3286G>T (p.Asp1096Tyr) variant in MYH7 has been identified in 0.023% (FAF 95% CI; 40/129162) of European chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BS1; Kelly 2018 PMID:29300372). Allowing a variant to reach a likely benign classification based on BS1 alone represents a revision of the original ACMG/AMP framework by ClinGen’s Sequence Variant Interpretation Working Group (Tavtigian 2018 PMID: 29300386). Additionally, while computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3), this pathogenic evidence code (PP3) was not considered to be in conflict with a likely benign conclusion given the accuracy of computation prediction tools. In summary, this variant meets criteria to be classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PP3, BS1 (less)
|
|
Uncertain significance
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1S
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440771.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
|
|
Uncertain significance
(Oct 30, 2019)
|
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: SCV002042664.1
First in ClinVar: Jan 01, 2022 Last updated: Jan 01, 2022 |
|
|
Uncertain Significance
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004814401.1
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 aspartic acid with tyrosine at codon 1096 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact … (more)
This missense variant replaces aspartic acid with tyrosine at codon 1096 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in several individuals affected with cardiomyopathy (PMID: 19412328, 27247418, 25031304, 32659924, 32746648, 32880476). This variant has also been identified in 40/282846 chromosomes (40/129122 non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Although the variant allele frequency is greater than expected for MYH7-related disorders based on prevalence, penetrance, and allelic heterogeneity, 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)
Number of individuals with the variant: 59
|
|
Likely Benign
(Nov 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Primary dilated cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059497.6
First in ClinVar: May 03, 2013 Last updated: Apr 20, 2024 |
Comment:
The p.Asp1096Tyr variant in MYH7 has been previously reported in >3 individuals with DCM left ventricular hypertrophy (Hershberger 2008 PMID: 19412328, Helms 2014 PMID: 25031304, … (more)
The p.Asp1096Tyr variant in MYH7 has been previously reported in >3 individuals with DCM left ventricular hypertrophy (Hershberger 2008 PMID: 19412328, Helms 2014 PMID: 25031304, LMM data). This variant has also been identified in 0.026% (18/68042) European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Likely Benign on Mar 22, 2021 by the ClinGen-approved Cardiomyopathy variant curation expert panel (Variation ID 42953). Given the frequency, this variant is classified as likely benign. ACMG/AMP Criteria applied: BS1, PP3. (less)
|
|
Uncertain significance
(Jan 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001149179.23
First in ClinVar: Feb 03, 2020 Last updated: Jun 17, 2024 |
Number of individuals with the variant: 1
|
|
Benign
(May 21, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1S
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001272028.1
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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
|
|
Benign
(May 21, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
MYH7-related skeletal myopathy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001272029.1
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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
|
|
Uncertain significance
(May 21, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Myosin storage myopathy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001272030.1
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)
|
|
Uncertain significance
(Nov 17, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
see cases
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations
Accession: SCV001443279.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
We observed a genetic variant c.3286G>T (p.D1096Y) in a male 68-y.o. patient diagnosed with left ventricular non-compaction and heart rhythm disorders. The p.D1096Y variant has … (more)
We observed a genetic variant c.3286G>T (p.D1096Y) in a male 68-y.o. patient diagnosed with left ventricular non-compaction and heart rhythm disorders. The p.D1096Y variant has a frequency of 1.414e-4 in gnomAD. The variant was detected in a MYH7 gene with z-score of 3.93, therefore intolerant to missense variants. Online in silico tools (PolyPhen2, MutationTaster, SIFT) predict the variant to be deleterious. However, in the absence of family screening results and the data on functional effects, we could only classify the p.D1096Y variant as the variant of uncertain clinical significance. (less)
Clinical Features:
Left ventricular noncompaction cardiomyopathy (present) , Ventricular arrhythmia (present) , Primary dilated cardiomyopathy (present) , Abnormal left ventricular function (present)
Age: 60-69 years
Sex: male
|
|
Likely benign
(Apr 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000208535.11
First in ClinVar: Feb 24, 2015 Last updated: Jul 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 23299917, 25163546, 32659924, 22337857, 23403236, 18555187, 27247418, 25031304, 19412328, 26383716, 27688314, 29300372, 28798025, 31737537, 28588093, 32528171, … (more)
This variant is associated with the following publications: (PMID: 23299917, 25163546, 32659924, 22337857, 23403236, 18555187, 27247418, 25031304, 19412328, 26383716, 27688314, 29300372, 28798025, 31737537, 28588093, 32528171, 32880476) (less)
|
|
Uncertain significance
(Mar 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
MYH7-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004115300.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The MYH7 c.3286G>T variant is predicted to result in the amino acid substitution p.Asp1096Tyr. This variant has been reported in individuals with dilated cardiomyopathy (Hershberger … (more)
The MYH7 c.3286G>T variant is predicted to result in the amino acid substitution p.Asp1096Tyr. This variant has been reported in individuals with dilated cardiomyopathy (Hershberger et al. 2008. PubMed ID: 19412328, Table 2), individuals with hypertrophic cardiomyopathy (Table S2 - Helms et al. 2014. PubMed ID: 25031304; Dataset S1 - Homburger. 2016. PubMed ID: 27247418), and an individual with left ventricular noncompaction (Table S3 - Miszalski-Jamka et al. 2017. PubMed ID: 28798025). However, it has also been reported in presumably healthy controls (Andreasen et al. 2013. PubMed ID: 23299917; Dataset S1 - Homburger. 2016. PubMed ID: 27247418). This variant is reported in 0.031% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-23890217-C-A). In ClinVar, this variant has conflicting interpretations of pathogenicity ranging from benign to uncertain including likely benign by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/42953/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
|
|
Uncertain significance
(Mar 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003817701.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
Uncertain significance
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000623693.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1096 of the MYH7 protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1096 of the MYH7 protein (p.Asp1096Tyr). This variant is present in population databases (rs45478699, gnomAD 0.03%). This missense change has been observed in individual(s) with cardiomyopathy (PMID: 19412328, 25031304, 25163446, 27247418, 28798025, 29300372). ClinVar contains an entry for this variant (Variation ID: 42953). 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%. 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)
|
|
Likely benign
(Jun 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000736672.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
|
|
Uncertain significance
(Jul 30, 2015)
|
criteria provided, single submitter
Method: research
|
Hypertrophic cardiomyopathy 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
Accession: SCV000256636.2
First in ClinVar: Nov 15, 2015 Last updated: Nov 15, 2015 |
Comment:
The Asp1096Tyr variant in MYH7 has been previously reported by Hershberger et al (2008) in 2 DCM probands. Helms et al (2014) analysed sarcomere transcript … (more)
The Asp1096Tyr variant in MYH7 has been previously reported by Hershberger et al (2008) in 2 DCM probands. Helms et al (2014) analysed sarcomere transcript and protein levels in septal myectomy and transplant specimens from genotyped HCM patients - one of whome carried this MYH Asp1096Tyr variant. This variant has been reported with an allele frequency of 0.0001 (18/66,720 European non-Finnish alleles and 1/908 'other') in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). The MYH7 Asp1096Tyr variant occurs in a conserved region, and in-silico tools (SIFT, PolyPhen, MutationTaster and CADD) support a damaging role for this variant, however this alone is not strong evidence for pathogenicity. We have identified this variant in 1 HCM proband who presented in her 30's with asymmetric hypertrophy (IVS 21mm) and obstruction. This proband experienced a sudden cardiac death in her 50s. It is noted that this proband also carried a pathogenic MYBPC3 nonsense variant. Based on the limited reports in the literature, and our finding of MYH7 Asp1096Tyr in an isolated HCM case who carried an additional variant which is known to be disease-causing, we have classified this variant as having "uncertain significance". Additional evidence is required to fully establish its pathogenic role. (less)
|
|
Likely pathogenic
(Oct 01, 2016)
|
criteria provided, single submitter
Method: research
|
Dilated cardiomyopathy
Affected status: no
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: CSER - NEXT Medicine variant annotation
Accession: SCV000700123.1 First in ClinVar: Mar 23, 2018 Last updated: Mar 23, 2018 |
Comment:
Found in patient having exome sequencing for an unrelated indication. No known history of dilated cardiomyopathy. This interpretation considers GERP score and allele frequency data, … (more)
Found in patient having exome sequencing for an unrelated indication. No known history of dilated cardiomyopathy. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review. (less)
|
|
Uncertain significance
(Jan 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000913719.5
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces aspartic acid with tyrosine at codon 1096 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact … (more)
This missense variant replaces aspartic acid with tyrosine at codon 1096 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in several individuals affected with cardiomyopathy (PMID: 19412328, 27247418, 25031304, 32659924, 32746648, 32880476). This variant has also been identified in 40/282846 chromosomes (40/129122 non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Although the variant allele frequency is greater than expected for MYH7-related disorders based on prevalence, penetrance, and allelic heterogeneity, 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)
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549878.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The MYH7 p.Asp1096Tyr variant was identified in 4 of 1006 proband chromosomes (frequency: 0.00398) from individuals with dilated cardiomyopathy (DCM) or left ventricular non-compaction (LVNC) … (more)
The MYH7 p.Asp1096Tyr variant was identified in 4 of 1006 proband chromosomes (frequency: 0.00398) from individuals with dilated cardiomyopathy (DCM) or left ventricular non-compaction (LVNC) and was not identified in 506 control chromosomes from healthy individuals (Hershberger_2008_PMID:19412328; Miszalski-Jamka_2017_PMID:28798025). The variant was identified in dbSNP (ID: rs45478699) and ClinVar (classified as uncertain significance by Invitae, Laboratory for Molecular Medicine, ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel and five other laboratories, and classified as likely pathogenic by CSER_CC_NCGL; University of Washington Medical Center). The variant was identified in control databases in 40 of 282846 chromosomes at a frequency of 0.0001414 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 40 of 129162 chromosomes (freq: 0.00031), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Asp1096 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
|
|
Uncertain significance
(May 01, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Dilated cardiomyopathy 1S
Affected status: yes
Allele origin:
germline
|
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen
Accession: SCV000298099.1
First in ClinVar: Jun 25, 2017 Last updated: Jun 25, 2017 |
Number of individuals with the variant: 1
|
|
Uncertain significance
(-)
|
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: SCV002037378.1 First in ClinVar: Dec 21, 2021 Last updated: Dec 21, 2021 |
|
|
Uncertain significance
(-)
|
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: SCV002034980.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 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 |
---|---|---|---|---|
Implications of Genetic Testing in Dilated Cardiomyopathy. | Verdonschot JAJ | Circulation. Genomic and precision medicine | 2020 | PMID: 32880476 |
Clinically relevant endothelial nitric oxide synthase polymorphisms and their impact on drug response. | Cotta Filho CK | Expert opinion on drug metabolism & toxicology | 2020 | PMID: 32746648 |
New Insights on Genetic Diagnostics in Cardiomyopathy and Arrhythmia Patients Gained by Stepwise Exome Data Analysis. | Kolokotronis K | Journal of clinical medicine | 2020 | PMID: 32659924 |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness. | Töpf A | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32528171 |
Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. | Kelly MA | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29300372 |
Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction. | Miszalski-Jamka K | Circulation. Cardiovascular genetics | 2017 | PMID: 28798025 |
Implantable Cardioverter-Defibrillator Therapy in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Predictors of Appropriate Therapy, Outcomes, and Complications. | Orgeron GM | Journal of the American Heart Association | 2017 | PMID: 28588093 |
Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy. | Helms AS | Circulation | 2016 | PMID: 27688314 |
Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation. | Homburger JR | Proceedings of the National Academy of Sciences of the United States of America | 2016 | PMID: 27247418 |
Atlas of the clinical genetics of human dilated cardiomyopathy. | Haas J | European heart journal | 2015 | PMID: 25163546 |
Metabolic engineering of Corynebacterium glutamicum for the production of L-ornithine. | Kim SY | Biotechnology and bioengineering | 2015 | PMID: 25163446 |
Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy. | Helms AS | Circulation. Cardiovascular genetics | 2014 | PMID: 25031304 |
Roadmap to determine the point mutations involved in cardiomyopathy disorder: a Bayesian approach. | Kumar A | Gene | 2013 | PMID: 23403236 |
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 |
Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. | Norton N | Circulation. Cardiovascular genetics | 2012 | PMID: 22337857 |
Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. | Hershberger RE | Clinical and translational science | 2008 | PMID: 19412328 |
Bioinformatics assessment of beta-myosin mutations reveals myosin's high sensitivity to mutations. | Buvoli M | Trends in cardiovascular medicine | 2008 | PMID: 18555187 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8b156efb-afd3-4dd9-9602-39a13d32a5b6 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs45478699 ...
HelpRecord last updated Jun 23, 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.