ClinVar Genomic variation as it relates to human health
NM_021625.5(TRPV4):c.958C>T (p.Arg320Ter)
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(4); Likely benign(7)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_021625.5(TRPV4):c.958C>T (p.Arg320Ter)
Variation ID: 469047 Accession: VCV000469047.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.11 12: 109798808 (GRCh38) [ NCBI UCSC ] 12: 110236613 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 26, 2017 Feb 4, 2024 Aug 4, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_021625.5:c.958C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_067638.3:p.Arg320Ter nonsense NM_001177428.1:c.817C>T NP_001170899.1:p.Arg273Ter nonsense NM_001177431.1:c.856C>T NP_001170902.1:p.Arg286Ter nonsense NM_001177433.1:c.817C>T NP_001170904.1:p.Arg273Ter nonsense NM_147204.2:c.958C>T NP_671737.1:p.Arg320Ter nonsense NC_000012.12:g.109798808G>A NC_000012.11:g.110236613G>A NG_017090.1:g.39600C>T LRG_372:g.39600C>T LRG_372t1:c.958C>T LRG_372p1:p.Arg320Ter - Protein change
- R320*, R286*, R273*
- Other names
- -
- Canonical SPDI
- NC_000012.12:109798807:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD) 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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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TRPV4 | - | - |
GRCh38 GRCh37 |
1128 | 1143 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Aug 4, 2022 | RCV000551761.12 | |
Uncertain significance (1) |
no assertion criteria provided
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Aug 14, 2019 | RCV000856931.1 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 11, 2017 | RCV001109833.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 11, 2017 | RCV001109834.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 11, 2017 | RCV001109835.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 11, 2017 | RCV001109837.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 11, 2017 | RCV001109836.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV001173240.1 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Aug 4, 2022 | RCV001508337.11 | |
Likely benign (1) |
criteria provided, single submitter
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Nov 25, 2019 | RCV002384176.1 |
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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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Brachyrachia (short spine dysplasia)
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001267209.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Metatropic dysplasia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001267210.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Scapuloperoneal spinal muscular atrophy
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001267212.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Spondylometaphyseal dysplasia, Kozlowski type
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001267213.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Neuronopathy, distal hereditary motor, autosomal dominant 8
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001267211.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jul 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease axonal type 2C
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001271662.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, London Health Sciences Centre
Accession: SCV001336322.1
First in ClinVar: Jun 14, 2020 Last updated: Jun 14, 2020 |
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Uncertain significance
(Jul 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714415.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Number of individuals with the variant: 1
|
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Likely benign
(Nov 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002695652.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: 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)
Number of individuals with the variant: 1
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Uncertain significance
(Aug 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease axonal type 2C
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000646258.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg320*) in the TRPV4 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg320*) in the TRPV4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TRPV4 cause disease. This variant is present in population databases (rs142902080, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with TRPV4-related conditions (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 469047). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Aug 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003821546.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Aug 14, 2019)
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no assertion criteria provided
Method: research
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Charcot-Marie-Tooth disease type 4
Affected status: yes
Allele origin:
germline
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Genesis Genome Database
Accession: SCV000999495.1
First in ClinVar: Dec 06, 2019 Last updated: Dec 06, 2019 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809076.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958790.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. | Volodarsky M | Journal of medical genetics | 2021 | PMID: 32376792 |
Text-mined citations for rs142902080 ...
HelpRecord last updated Mar 17, 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.