NM_003001.5(SDHC):c.474_477del (p.Thr159fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 28, 2022
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:: RCV003041801.3

Allele description [Variation Report for NM_003001.5(SDHC):c.474_477del (p.Thr159fs)]

NM_003001.5(SDHC):c.474_477del (p.Thr159fs)

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.474_477del (p.Thr159fs)

HGVS:

NC_000001.11:g.161362397_161362400del
NG_012767.1:g.53022_53025del
NM_001035511.3:c.310_313delTACT
NM_001035512.3:c.372_375delTACT
NM_001035513.3:c.315_318delTACT
NM_001278172.3:c.208_211delTACT
NM_001407115.1:c.594_597delTACT
NM_001407116.1:c.417_420delTACT
NM_001407117.1:c.411_414delTACT
NM_001407118.1:c.366_369delTACT
NM_001407119.1:c.363_366delTACT
NM_001407120.1:c.363_366delTACT
NM_001407121.1:c.253_256delTACT
NM_003001.5:c.474_477delMANE SELECT
NP_001030588.1:p.Tyr104Valfs
NP_001030588.1:p.Tyr104fs
NP_001030589.1:p.Thr125Cysfs
NP_001030589.1:p.Thr125fs
NP_001030590.1:p.Thr106Cysfs
NP_001030590.1:p.Thr106fs
NP_001265101.1:p.Tyr70Valfs
NP_001265101.1:p.Tyr70fs
NP_001394044.1:p.Thr199Cysfs
NP_001394045.1:p.Thr140Cysfs
NP_001394046.1:p.Thr138Cysfs
NP_001394047.1:p.Thr123Cysfs
NP_001394048.1:p.Thr122Cysfs
NP_001394049.1:p.Thr122Cysfs
NP_001394050.1:p.Tyr85Valfs
NP_002992.1:p.Thr159Cysfs
NP_002992.1:p.Thr159fs
LRG_317t1:c.474_477del
LRG_317:g.53022_53025del
LRG_317p1:p.Thr159Cysfs
NC_000001.10:g.161332185_161332188del
NC_000001.10:g.161332187_161332190del
NM_001035511.2:c.310_313del
NM_001035512.2:c.372_375del
NM_001035513.2:c.315_318del
NM_001278172.2:c.208_211del
NM_003001.3:c.474_477delTACT
NR_103459.2:n.526_529del
NR_103459.3:n.526_529delTACT

Protein change:

T106fs

Molecular consequence:

NM_001035511.3:c.310_313delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001035512.3:c.372_375delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001035513.3:c.315_318delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001278172.3:c.208_211delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407115.1:c.594_597delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407116.1:c.417_420delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407117.1:c.411_414delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407118.1:c.366_369delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407119.1:c.363_366delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407120.1:c.363_366delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407121.1:c.253_256delTACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003001.5:c.474_477del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003316143	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003316143

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 28, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003316143.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This frameshift has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndromes (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the SDHC gene (p.Thr159Cysfs*111). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the SDHC protein and extend the protein by 99 additional amino acid residues.

#	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: Apr 15, 2024

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