ClinVar Genomic variation as it relates to human health
NM_003001.5(SDHC):c.386G>A (p.Trp129Ter)
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
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NM_003001.5(SDHC):c.386G>A (p.Trp129Ter)
Variation ID: 978229 Accession: VCV000978229.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q23.3 1: 161356821 (GRCh38) [ NCBI UCSC ] 1: 161326611 (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 Sep 24, 2020 Feb 28, 2024 Jul 26, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003001.5:c.386G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002992.1:p.Trp129Ter nonsense NM_001035511.3:c.242-5508G>A intron variant NM_001035512.3:c.284G>A NP_001030589.1:p.Trp95Ter nonsense NM_001035513.3:c.227G>A NP_001030590.1:p.Trp76Ter nonsense NM_001278172.3:c.140-5508G>A intron variant NM_001407115.1:c.506G>A NP_001394044.1:p.Trp169Ter nonsense NM_001407116.1:c.329G>A NP_001394045.1:p.Trp110Ter nonsense NM_001407117.1:c.323G>A NP_001394046.1:p.Trp108Ter nonsense NM_001407118.1:c.278G>A NP_001394047.1:p.Trp93Ter nonsense NM_001407119.1:c.275G>A NP_001394048.1:p.Trp92Ter nonsense NM_001407120.1:c.275G>A NP_001394049.1:p.Trp92Ter nonsense NM_001407121.1:c.185-5508G>A intron variant NR_103459.3:n.438G>A non-coding transcript variant NC_000001.11:g.161356821G>A NC_000001.10:g.161326611G>A NG_012767.1:g.47446G>A LRG_317:g.47446G>A LRG_317t1:c.386G>A LRG_317p1:p.Trp129Ter - Protein change
- W129*, W76*, W95*, W108*, W169*, W92*, W110*, W93*
- Other names
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- Canonical SPDI
- NC_000001.11:161356820:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- protein truncation Variation Ontology [VariO:0015]
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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
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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SDHC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
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Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (1) |
criteria provided, single submitter
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Jul 15, 2020 | RCV001256199.3 | |
Likely pathogenic (1) |
no assertion criteria provided
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Sep 1, 2020 | RCV001257556.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 26, 2022 | RCV001879958.5 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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
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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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Pathogenic
(Jul 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Paragangliomas 3
(Autosomal dominant inheritance)
Affected status: yes, no
Allele origin:
germline
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Department of Medical Genetics, College of Basic Medicine, Army Medical University
Accession: SCV001422317.1
First in ClinVar: Sep 24, 2020 Last updated: Sep 24, 2020 |
Comment:
The Trp129Ter variant in SDHC creates a premature nonsense codon, which has been reported in ClinVar as Pathogenic in Hereditary cancer-predisposing syndrome. This variant was … (more)
The Trp129Ter variant in SDHC creates a premature nonsense codon, which has been reported in ClinVar as Pathogenic in Hereditary cancer-predisposing syndrome. This variant was found in a Chinese patient with Paragangliomas and the data is high quality. (less)
Observation 1:
Number of individuals with the variant: 3
Age: 5-63 years
Sex: female
Ethnicity/Population group: East Asian
Geographic origin: Southwest of China
Observation 2:
Clinical Features:
Hypertensive disorder (present) , Paragangliomas (present)
Age: 30-39 years
Sex: male
Ethnicity/Population group: East Asian
Geographic origin: Southwest of China
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Pathogenic
(Jul 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Paragangliomas 3
Gastrointestinal stromal tumor
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
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Invitae
Accession: SCV002233571.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, … (more)
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SDHC protein in which other variant(s) (p.Arg133*) have been determined to be pathogenic (PMID: 23083876, 24423348, 24758179, 27700540). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 978229). This premature translational stop signal has been observed in individual(s) with rhabdomyosarcoma (PMID: 33372952). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp129*) in the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the SDHC protein. (less)
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Likely pathogenic
(Sep 01, 2020)
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no assertion criteria provided
Method: provider interpretation
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Rhabdomyosarcoma
Affected status: yes
Allele origin:
germline
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Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434382.1
First in ClinVar: Oct 02, 2020 Last updated: Oct 02, 2020 |
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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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
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This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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protein truncation
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Department of Medical Genetics, College of Basic Medicine, Army Medical University
Accession: SCV001422317.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group. | Li H | Journal of the National Cancer Institute | 2021 | PMID: 33372952 |
A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL. | Bourdeau I | The Journal of clinical endocrinology and metabolism | 2016 | PMID: 27700540 |
The clinical phenotype of SDHC-associated hereditary paraganglioma syndrome (PGL3). | Else T | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 24758179 |
Phenotypic variability and risk of malignancy in SDHC-linked paragangliomas: lessons from three unrelated cases with an identical germline mutation (p.Arg133*). | Bickmann JK | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 24423348 |
Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer. | Ricketts CJ | The Journal of urology | 2012 | PMID: 23083876 |
Text-mined citations for rs1672294906 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.