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:: RCV000691372.11

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

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:: Pheochromocytoma/paraganglioma syndrome 3
Synonyms:: GLOMUS TUMORS, FAMILIAL, 3; Paragangliomas 3; SDHC-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 3); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011544; MedGen: C1854336; Orphanet: 29072; OMIM: 605373

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819148	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 8, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17576681, 9536098, 17667967, 24402737, 24758179, 12658451, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819148

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 8, 2019)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819148.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

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. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 16, 2026

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