ClinVar Genomic variation as it relates to human health
NM_003002.4(SDHD):c.170-1G>T
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_003002.4(SDHD):c.170-1G>T
Variation ID: 438434 Accession: VCV000438434.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.1 11: 112088866 (GRCh38) [ NCBI UCSC ] 11: 111959590 (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 15, 2017 Apr 20, 2024 Jan 11, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003002.4:c.170-1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001276503.2:c.169+893G>T intron variant NM_001276504.2:c.53-1G>T splice acceptor NM_001276506.2:c.170-1G>T splice acceptor NC_000011.10:g.112088866G>T NC_000011.9:g.111959590G>T NG_012337.3:g.7020G>T NG_033145.1:g.2933C>A LRG_9:g.7020G>T LRG_9t1:c.170-1G>T - Protein change
- Other names
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- Canonical SPDI
- NC_000011.10:112088865:G:T
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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 0.00000
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
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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SDHD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
642 | 778 |
Conditions - Germline
Condition
Help
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
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
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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 (2) |
criteria provided, single submitter
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Jun 20, 2023 | RCV000505295.9 | |
Pathogenic (1) |
criteria provided, single submitter
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May 6, 2020 | RCV002413385.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2024 | RCV002524414.9 |
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
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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
(May 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002715773.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The c.170-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 3 of the SDHD gene. This alteration … (more)
The c.170-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 3 of the SDHD gene. This alteration has been identified in numerous patients from multiple ethnic groups with unilateral or bilateral carotid body tumors, both with and without a family history of pheochromocytomas and/or paragangliomas (Dannenberg H et al. Clin. Cancer Res. 2002 Jul;8:2061-6; Persu A et al. J. Hypertens. 2008 Jul;26:1395-401; Renard L et al. Head Neck. 2003 Feb;25:146-51; Zuo Y et al. Urology. 2018 06;116:63-67; Santi R et al. Anticancer Res. 2017 02;37:805-812; Piccini V et al. Endocr. Relat. Cancer. 2012 Apr;19:149-55; Burnichon N et al. J. Clin. Endocrinol. Metab. 2009 Aug;94:2817-27; Astrom K et al. Hum. Genet. 2003 Aug;113:228-37; Benn DE et al. J. Clin. Endocrinol. Metab. 2006 Mar;91:827-36). This alteration was also identified in a patient with a glomus tumor (Mannelli M et al. Ann. N. Y. Acad. Sci. 2006 Aug;1073:183-9), a patient with bilateral carotid body tumors and a primary mediastinal paraganglioma (Ghayee HK et al. Endocr. Relat. Cancer. 2009 Mar;16:291-9;), and patients with cervical paragangliomas (Bauters C et al. J. Med. Genet. 2003 Jun;40:e75). Of note, this alteration is also designated as IVS2-1G>T in the published literature. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jan 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Carney-Stratakis syndrome
Paragangliomas with sensorineural hearing loss Pheochromocytoma Cowden syndrome 3
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: SCV000762655.4
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 2 of the SDHD gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 2 of the SDHD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). This variant is present in population databases (no rsID available, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with SDHD-related conditions (PMID: 12114404, 12509798, 18551016, 19075037, 22566194, 29545045, 30050099, 30877234). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 438434). 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. (less)
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Pathogenic
(Jun 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pheochromocytoma-paraganglioma
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004828417.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
This variant disrupts a canonical splice site and is predicted to result in abnormal splicing. Aberrant splicing and/or loss of function is an established mechanism … (more)
This variant disrupts a canonical splice site and is predicted to result in abnormal splicing. Aberrant splicing and/or loss of function is an established mechanism of disease. This prediction has been confirmed by functional studies (PMID: 12509798, 29545045). This variant has been reported in multiple individuals with paragangliomas (PMID: 12509798, 18551016, 12114404, 19075037, 22566194, 29545045, 30877234, 32472550). This variant is present in 1/251124 total alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant has been reported to co-segregate with disease in more than one family (PMID: 12509798, 18551016, 32472550). (less)
Number of individuals with the variant: 1
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Hereditary pheochromocytoma-paraganglioma
Affected status: yes
Allele origin:
germline
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Section on Medical Neuroendocrinolgy, National Institutes of Health
Accession: SCV000599538.1
First in ClinVar: Sep 15, 2017 Last updated: Sep 15, 2017 |
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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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[Identification of SDHD c.170-1G>T variant in pedigree affected with carotid body tumor]. | Liu H | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2020 | PMID: 32472550 |
Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma. | Ben Aim L | Journal of medical genetics | 2019 | PMID: 30877234 |
Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma. | Richter S | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30050099 |
Multifocal Paraganglioma and Pheochromocytoma Due to Truncated SDHD Mutation. | Zuo Y | Urology | 2018 | PMID: 29545045 |
Potential Pitfalls of SDH Immunohistochemical Detection in Paragangliomas and Phaeochromocytomas Harbouring Germline SDHx Gene Mutation. | Santi R | Anticancer research | 2017 | PMID: 28179334 |
Prevalence and spectrum of SDHx mutations in pheochromocytoma and paraganglioma in patients from Belgium: an update. | Persu A | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme | 2012 | PMID: 22566194 |
Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients. | Piccini V | Endocrine-related cancer | 2012 | PMID: 22241717 |
Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. | Ricketts CJ | Human mutation | 2010 | PMID: 19802898 |
The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. | Burnichon N | The Journal of clinical endocrinology and metabolism | 2009 | PMID: 19454582 |
Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior. | Ghayee HK | Endocrine-related cancer | 2009 | PMID: 19075037 |
High prevalence of SDHB mutations in head and neck paraganglioma in Belgium. | Persu A | Journal of hypertension | 2008 | PMID: 18551016 |
SDH mutations in patients affected by paraganglioma syndromes: a personal experience. | Mannelli M | Annals of the New York Academy of Sciences | 2006 | PMID: 17102085 |
Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. | Benn DE | The Journal of clinical endocrinology and metabolism | 2006 | PMID: 16317055 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect. | Astrom K | Human genetics | 2003 | PMID: 12811540 |
Hereditary phaeochromocytomas and paragangliomas: a study of five susceptibility genes. | Bauters C | Journal of medical genetics | 2003 | PMID: 12807974 |
A novel mutation in the SDHD gene in a family with inherited paragangliomas--implications of genetic diagnosis for follow up and treatment. | Renard L | Head & neck | 2003 | PMID: 12509798 |
Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma. | Dannenberg H | Clinical cancer research : an official journal of the American Association for Cancer Research | 2002 | PMID: 12114404 |
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Text-mined citations for rs1306475361 ...
HelpRecord last updated Apr 20, 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.