ClinVar Genomic variation as it relates to human health
NM_001267550.2(TTN):c.98390A>G (p.Asn32797Ser)
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(2); Benign(10); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001267550.2(TTN):c.98390A>G (p.Asn32797Ser)
Variation ID: 47600 Accession: VCV000047600.69
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q31.2 2: 178539675 (GRCh38) [ NCBI UCSC ] 2: 179404402 (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 Jul 6, 2014 May 12, 2024 Apr 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001267550.2:c.98390A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001254479.2:p.Asn32797Ser missense NM_001256850.1:c.93467A>G NP_001243779.1:p.Asn31156Ser missense NM_003319.4:c.71195A>G NP_003310.4:p.Asn23732Ser missense NM_133378.4:c.90686A>G NP_596869.4:p.Asn30229Ser missense NM_133432.3:c.71570A>G NP_597676.3:p.Asn23857Ser missense NM_133437.4:c.71771A>G NP_597681.4:p.Asn23924Ser missense NR_038272.1:n.1625T>C non-coding transcript variant NC_000002.12:g.178539675T>C NC_000002.11:g.179404402T>C NG_011618.3:g.296128A>G NG_051363.1:g.21849T>C LRG_391:g.296128A>G LRG_391t1:c.98390A>G LRG_391p1:p.Asn32797Ser - Protein change
- N32797S, N30229S, N31156S, N23732S, N23857S, N23924S
- Other names
- p.N31156S:AAC>AGC
- Canonical SPDI
- NC_000002.12:178539674:T:C
-
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.
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0.00399 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00375
1000 Genomes Project 0.00399
Exome Aggregation Consortium (ExAC) 0.00436
The Genome Aggregation Database (gnomAD), exomes 0.00449
The Genome Aggregation Database (gnomAD) 0.00504
Trans-Omics for Precision Medicine (TOPMed) 0.00555
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00576
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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TTN | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
11725 | 31212 | |
TTN-AS1 | - | - | - | GRCh38 | - | 17885 |
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. |
---|---|---|---|---|
Benign/Likely benign (10) |
criteria provided, multiple submitters, no conflicts
|
Oct 19, 2020 | RCV000040869.45 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2024 | RCV000419770.39 | |
Benign (1) |
criteria provided, single submitter
|
Sep 18, 2015 | RCV000621374.11 | |
Likely benign (1) |
criteria provided, single submitter
|
Jul 14, 2017 | RCV000768846.10 | |
Benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001082901.15 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001129725.12 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001129726.12 | |
Benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001132433.12 | |
Benign (1) |
criteria provided, single submitter
|
Oct 17, 2018 | RCV000852783.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001132434.12 | |
Benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001132435.12 | |
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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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Benign
(Jan 31, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000169444.11
First in ClinVar: Jun 23, 2014 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Likely benign
(Aug 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000064560.6
First in ClinVar: May 03, 2013 Last updated: May 03, 2018 |
Comment:
p.Asn30229Ser in exon 301 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.7% (866/125740) of European … (more)
p.Asn30229Ser in exon 301 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.7% (866/125740) of European chr omosomes, including 4 homozygotes, by the Genome Aggregation Database (gnomAD, h ttp://gnomad.broadinstitute.org; dbSNP rs149001703). (less)
Number of individuals with the variant: 24
|
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Benign
(Oct 19, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362714.2
First in ClinVar: Jun 22, 2020 Last updated: Nov 14, 2020 |
Comment:
Variant summary: TTN c.90686A>G (p.Asn30229Ser) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five … (more)
Variant summary: TTN c.90686A>G (p.Asn30229Ser) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0045 in 248154 control chromosomes, predominantly at a frequency of 0.0071 within the Non-Finnish European subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 11-fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Twelve ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign while one ClinVar submitter (evaluation after 2014) cites it as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. (less)
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Likely Benign
(Nov 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000510867.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Converted during submission to Likely benign.
|
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Benign
(Aug 10, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000333233.3
First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
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Benign
(Aug 29, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001146555.1
First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020 |
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000315614.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Likely benign
(Jul 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000900219.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019 |
|
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Benign
(Oct 17, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT Syndrome
Affected status: yes
Allele origin:
germline
|
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995506.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 2
|
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2J
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001289268.1
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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Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1G
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001289269.1
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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Myopathy, myofibrillar, 9, with early respiratory failure
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001292093.1
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
|
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Early-onset myopathy with fatal cardiomyopathy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001292094.1
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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Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Tibial muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001292095.1
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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
|
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Benign
(Oct 21, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156928.5
First in ClinVar: Feb 10, 2020 Last updated: Mar 04, 2023 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Dilated cardiomyopathy 1G
Autosomal recessive limb-girdle muscular dystrophy type 2J
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000286950.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
|
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Benign
(Sep 18, 2015)
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criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000735356.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
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Likely benign
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001152620.22
First in ClinVar: Feb 03, 2020 Last updated: May 12, 2024 |
Comment:
TTN: BP4, BS2
Number of individuals with the variant: 46
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000153411.2
First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014 |
Comment:
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more)
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932833.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002035765.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
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Likely benign
(-)
|
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: SCV001741399.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
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: SCV001924007.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
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: SCV001954914.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
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: SCV001974832.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 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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The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel. | Schweizer PA | Journal of the American College of Cardiology | 2014 | PMID: 25145518 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN | - | - | - | - |
Text-mined citations for rs149001703 ...
HelpRecord last updated May 12, 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.