NM_003002.4(SDHD):c.191_192del (p.Leu64fs) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000641035.1

Allele description [Variation Report for NM_003002.4(SDHD):c.191_192del (p.Leu64fs)]

NM_003002.4(SDHD):c.191_192del (p.Leu64fs)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.191_192del (p.Leu64fs)
HGVS:
  • NC_000011.10:g.112088884TC[2]
  • NG_012337.3:g.7038TC[2]
  • NG_033145.1:g.2910GA[2]
  • NM_001276503.2:c.169+911TC[2]
  • NM_001276504.2:c.74_75del
  • NM_001276506.2:c.191_192del
  • NM_003002.4:c.191_192delMANE SELECT
  • NP_001263433.1:p.Leu25fs
  • NP_001263435.1:p.Leu64fs
  • NP_002993.1:p.Leu64fs
  • LRG_9t1:c.191_192del
  • LRG_9:g.7038TC[2]
  • LRG_9p1:p.Leu64fs
  • NC_000011.9:g.111959608TC[2]
  • NG_012337.2:g.7042_7043del
  • NM_003002.2:c.191_192delTC
  • NM_003002.3:c.191_192delTC
  • NR_077060.2:n.222TC[2]
Protein change:
L25fs
Links:
OMIM: 602690.0013; dbSNP: rs387906358
NCBI 1000 Genomes Browser:
rs387906358
Molecular consequence:
  • NM_001276504.2:c.74_75del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276506.2:c.191_192del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003002.4:c.191_192del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276503.2:c.169+911TC[2] - intron variant - [Sequence Ontology: SO:0001627]
  • NR_077060.2:n.222TC[2] - 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 1 (PGL1)
Synonyms:
PARAGANGLIOMA, CAROTID BODY; PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; See all synonyms [MedGen]
Identifiers:
MedGen: C1868633; Orphanet: 29072; OMIM: 168000
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000762653Invitaecriteria provided, single submitter
Pathogenic
(Dec 1, 2017)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features.

Badenhop RF, Jansen JC, Fagan PA, Lord RS, Wang ZG, Foster WJ, Schofield PR.

J Med Genet. 2004 Jul;41(7):e99. No abstract available.

PubMed [citation]
PMID:
15235042
PMCID:
PMC1735850
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000762653.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Leu64Profs*4) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported  in the literature in individuals and families affected with paraganglioma, and segregates with disease in at lease one family (PMID: 11391796, 15235042, 19454582, 23902947). ClinVar contains an entry for this variant (Variation ID: 6904). Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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