This sequence change affects the initiator methionine of the SDHD mRNA. The next in-frame methionine is located at codon 91. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with head and neck paragangliomas (HNPGLs) or non-HNPGLs (PMID: 11391796, 15066320, 17576205, 19351833, 19454582, 21945342, 22241717). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6911). For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, single submitter
- Submissions:
- 2
- First in ClinVar:
- Apr 17, 2017
- Most recent Submission:
- Sep 3, 2023
- Last evaluated:
- Feb 17, 2022
- Accession:
- VCV000006911.14
- Variation ID:
- 6911
- Description:
- single nucleotide variant
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NM_003002.4(SDHD):c.1A>G (p.Met1Val)
- Allele ID
- 21950
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 11q23.1
- Genomic location
- 11: 112086908 (GRCh38) GRCh38 UCSC
- 11: 111957632 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003002.4:c.1A>G MANE Select NP_002993.1:p.Met1Val missense initiator codon variant NM_001276503.2:c.1A>G NP_001263432.1:p.Met1Val missense initiator codon variant NM_001276504.2:c.1A>G NP_001263433.1:p.Met1Val missense initiator codon variant NM_001276506.2:c.1A>G NP_001263435.1:p.Met1Val missense initiator codon variant NR_077060.2:n.36A>G non-coding transcript variant NC_000011.10:g.112086908A>G NC_000011.9:g.111957632A>G NG_012337.3:g.5062A>G NG_033145.1:g.4891T>C LRG_9:g.5062A>G LRG_9t1:c.1A>G LRG_9p1:p.Met1Val - Protein change
- M1V
- Other names
- -
- Canonical SPDI
- NC_000011.10:112086907:A:G
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA016859
- OMIM: 602690.0021
- dbSNP: rs104894307
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | criteria provided, single submitter | Feb 17, 2022 | RCV002228010.8 | |
| Pathogenic | 1 | no assertion criteria provided | Apr 15, 2004 | RCV000007320.12 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| SDHD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
556 | 677 | |
| LOC126861339 | - | - | - | GRCh38 | - | 100 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Feb 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000554046.8
First in ClinVar: Apr 17, 2017 Last updated: Sep 03, 2023 |
Comment:
This sequence change affects the initiator methionine of the SDHD mRNA. The next in-frame methionine is located at codon 91. This variant is not present … (more)
This sequence change affects the initiator methionine of the SDHD mRNA. The next in-frame methionine is located at codon 91. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with head and neck paragangliomas (HNPGLs) or non-HNPGLs (PMID: 11391796, 15066320, 17576205, 19351833, 19454582, 21945342, 22241717). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6911). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 15, 2004)
|
no assertion criteria provided
Method: literature only
|
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000027518.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 03, 2023 |
Comment on evidence:
In tumor sections from 3 unrelated patients with sporadic carotid body paraganglioma (see 168000), 1 with multiple paragangliomas and 2 with single tumors, Riemann et … (more)
In tumor sections from 3 unrelated patients with sporadic carotid body paraganglioma (see 168000), 1 with multiple paragangliomas and 2 with single tumors, Riemann et al. (2004) performed sequence analysis of the SDHD gene and identified a 1A-G transition in exon 1, resulting in a met1-to-val (M1V) substitution in the initiation codon. LOH and FISH analyses demonstrated partial/total monosomy for chromosome 11 in the tumor samples tested. A mutation at the same codon, M1I (602690.0015), had previously been reported in cases of familial paraganglioma. (less)
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients. | Piccini V | Endocrine-related cancer | 2012 | PMID: 22241717 |
| Common genetic mutations in the start codon of the SDH subunit D gene among Chinese families with familial head and neck paragangliomas. | Wang CP | Oral oncology | 2012 | PMID: 21945342 |
| 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 |
| Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out. | Neumann HP | Cancer research | 2009 | PMID: 19351833 |
| Novel SDHD germ-line mutations in pheochromocytoma patients. | Neumayer C | European journal of clinical investigation | 2007 | PMID: 17576205 |
| Chromosome 11 monosomy in conjunction with a mutated SDHD initiation codon in nonfamilial paraganglioma cases. | Riemann K | Cancer genetics and cytogenetics | 2004 | PMID: 15066320 |
| Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss. | Badenhop RF | Genes, chromosomes & cancer | 2001 | PMID: 11391796 |
Text-mined citations for rs104894307...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 23, 2023