NM_003002.4(SDHD):c.49C>T (p.Arg17Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 2023
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:: RCV002540717.10

Allele description [Variation Report for NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)]

NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)

Genes:

LOC126861339:BRD4-independent group 4 enhancer GRCh37_chr11:111957035-111958234 [Gene]
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)

HGVS:

NC_000011.10:g.112086956C>T
NG_012337.3:g.5110C>T
NG_033145.1:g.4843G>A
NM_001276503.2:c.49C>T
NM_001276504.2:c.49C>T
NM_001276506.2:c.49C>T
NM_003002.4:c.49C>TMANE SELECT
NP_001263432.1:p.Arg17Ter
NP_001263433.1:p.Arg17Ter
NP_001263435.1:p.Arg17Ter
NP_002993.1:p.Arg17Ter
LRG_9t1:c.49C>T
LRG_9:g.5110C>T
LRG_9p1:p.Arg17Ter
NC_000011.9:g.111957680C>T
NM_001276503.1:c.49C>T
NM_003002.2:c.49C>T
NR_077060.2:n.84C>T

Protein change:

R17*

Links:

dbSNP: rs1314133983

NCBI 1000 Genomes Browser:

rs1314133983

Molecular consequence:

NR_077060.2:n.84C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001276503.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276504.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276506.2:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003002.4:c.49C>T - nonsense - [Sequence Ontology: SO:0001587]

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
Identifiers:: MedGen: C1868633

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441040	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19454582, 19802898, 18213727, 30050099, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441040

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2023)

germline

clinical testing

PubMed (5)
[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

Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD.

Ricketts CJ, Forman JR, Rattenberry E, Bradshaw N, Lalloo F, Izatt L, Cole TR, Armstrong R, Kumar VK, Morrison PJ, Atkinson AB, Douglas F, Ball SG, Cook J, Srirangalingam U, Killick P, Kirby G, Aylwin S, Woodward ER, Evans DG, Hodgson SV, Murday V, et al.

Hum Mutat. 2010 Jan;31(1):41-51. doi: 10.1002/humu.21136.

PubMed [citation]

PMID:: 19802898

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441040.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg17*) in the SDHD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with paraganglioma (PMID: 18213727, 30050099). ClinVar contains an entry for this variant (Variation ID: 1319258). For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 24, 2024

ClinVar

Relating variation to medicine