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NM_003001.5(SDHC):c.405+1del AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 8, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000691372.10

Allele description [Variation Report for NM_003001.5(SDHC):c.405+1del]

NM_003001.5(SDHC):c.405+1del

Gene:
SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1q23.3
Genomic location:
Preferred name:
NM_003001.5(SDHC):c.405+1del
HGVS:
  • NC_000001.10:g.161326630del
  • NC_000001.11:g.161356841del
  • NG_012767.1:g.47466del
  • NG_157433.1:g.231del
  • NM_001035511.3:c.242-5488del
  • NM_001035512.3:c.303+1del
  • NM_001035513.3:c.246+1del
  • NM_001278172.3:c.140-5488del
  • NM_001407115.1:c.525+1del
  • NM_001407116.1:c.348+1del
  • NM_001407117.1:c.342+1del
  • NM_001407118.1:c.297+1del
  • NM_001407119.1:c.294+1del
  • NM_001407120.1:c.294+1del
  • NM_001407121.1:c.185-5488del
  • NM_003001.5:c.405+1delMANE SELECT
  • LRG_317t1:c.405+1del
  • LRG_317:g.47466del
  • NC_000001.10:g.161326630del
  • NC_000001.10:g.161326630delG
  • NC_000001.10:g.161326631del
  • NM_003001.3:c.405+1del
  • NM_003001.3:c.405+1delG
Links:
dbSNP: rs1558182956
NCBI 1000 Genomes Browser:
rs1558182956
Molecular consequence:
  • NM_001035511.3:c.242-5488del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001278172.3:c.140-5488del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407121.1:c.185-5488del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001035512.3:c.303+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001035513.3:c.246+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407115.1:c.525+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407116.1:c.348+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407117.1:c.342+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407118.1:c.297+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407119.1:c.294+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407120.1:c.294+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_003001.5:c.405+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Gastrointestinal stromal tumor
Synonyms:
Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 3 (PPGL3)
Synonyms:
GLOMUS TUMORS, FAMILIAL, 3; SDHC-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 3); PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 3
Identifiers:
MONDO: MONDO:0011544; MedGen: C1854336; Orphanet: 29072; OMIM: 605373

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000819148Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 8, 2019) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819148.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects a donor splice site in the last intron (intron 5) of the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHC-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant affecting this nucleotide (c.405+1G>T) has been determined to be pathogenic (PMID: 17667967, 24402737, 24758179, 12658451). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025