NM_003002.4(SDHD):c.242del (p.Pro81fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 17, 2016
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:: RCV002229347.13

Allele description [Variation Report for NM_003002.4(SDHD):c.242del (p.Pro81fs)]

NM_003002.4(SDHD):c.242del (p.Pro81fs)

Gene:

SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_003002.4(SDHD):c.242del (p.Pro81fs)

HGVS:

NC_000011.10:g.112088939del
NC_000011.9:g.111959662del
NG_012337.3:g.7093del
NG_033145.1:g.2861del
NM_001276503.2:c.169+966del
NM_001276504.2:c.125del
NM_001276506.2:c.242del
NM_003002.4:c.242delMANE SELECT
NP_001263433.1:p.Pro42fs
NP_001263435.1:p.Pro81fs
NP_002993.1:p.Pro81fs
LRG_9t1:c.242del
LRG_9:g.7093del
LRG_9p1:p.Pro81fs
NC_000011.9:g.111959662del
NC_000011.9:g.111959662delC
NC_000011.9:g.111959663del
NM_003002.2:c.242delC
NM_003002.3:c.242delC
NR_077060.2:n.277del

Protein change:

P42fs

Links:

dbSNP: rs878854591

NCBI 1000 Genomes Browser:

rs878854591

Molecular consequence:

NM_001276504.2:c.125del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276506.2:c.242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003002.4:c.242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276503.2:c.169+966del - intron variant - [Sequence Ontology: SO:0001627]
NR_077060.2:n.277del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Carney-Stratakis syndrome
Synonyms:: Paraganglioma and gastric stromal sarcoma; Paraganglioma and gastrointestinal stromal tumor; Paraganglioma and GIST; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011740; MedGen: C1847319; Orphanet: 97286; OMIM: 606864

Name:: Pheochromocytoma
Synonyms:: Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

Name:: Paragangliomas with sensorineural hearing loss (PGL1)
Identifiers:: MedGen: C1868633

Name:: Cowden syndrome 3 (CWS3)
Identifiers:: MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001582234	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19454582, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582234

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2016)

germline

clinical testing

PubMed (2)
[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

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP; PGL.NET network..

J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub 2009 May 19.

PubMed [citation]

PMID:: 19454582

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, SCV001582234.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Truncating variants in SDHD are known to be pathogenic. This particular truncation has been reported in the literature in a patient affected with paraganglioma (PMID: 19454582). This variant is also referred to as c.242del* in the literature. This sequence change deletes 1 nucleotide from exon 3 of the SDHD mRNA (c.242delC), causing a frameshift at codon 81. This creates a premature translational stop signal (p.Pro81Argfs*5) and is expected to result in an absent or 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: May 26, 2024

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