NM_003002.4(SDHD):c.57del (p.Leu20fs) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Oct 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000641042.1

Allele description [Variation Report for NM_003002.4(SDHD):c.57del (p.Leu20fs)]

NM_003002.4(SDHD):c.57del (p.Leu20fs)

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.57del (p.Leu20fs)
HGVS:
  • NC_000011.10:g.112087861del
  • NG_012337.3:g.6015del
  • NG_033145.1:g.3938del
  • NM_001276503.2:c.57del
  • NM_001276504.2:c.52+902del
  • NM_001276506.2:c.57del
  • NM_003002.4:c.57delMANE SELECT
  • NP_001263432.1:p.Leu20fs
  • NP_001263435.1:p.Leu20fs
  • NP_002993.1:p.Leu20fs
  • LRG_9t1:c.57del
  • LRG_9:g.6015del
  • LRG_9p1:p.Leu20fs
  • NC_000011.9:g.111958585del
  • NG_012337.2:g.6015del
  • NM_003002.2:c.57del
  • NM_003002.2:c.57delG
  • NM_003002.3:c.57delG
  • NR_077060.2:n.92del
Protein change:
L20fs
Links:
OMIM: 602690.0027; dbSNP: rs587776649
NCBI 1000 Genomes Browser:
rs587776649
Molecular consequence:
  • NM_001276503.2:c.57del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276506.2:c.57del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003002.4:c.57del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276504.2:c.52+902del - intron variant - [Sequence Ontology: SO:0001627]
  • NR_077060.2:n.92del - 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:
PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; Paragangliomas familial 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
SCV000762660Invitaecriteria provided, single submitter
Pathogenic
(Oct 23, 2017)
germlineclinical testing

PubMed (2)
[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

Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD.

Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, Boikos SA, Ferrando B, Pacak K, Assie G, Baudin E, Chompret A, Ellison JW, Briere JJ, Rustin P, Gimenez-Roqueplo AP, Eng C, Carney JA, Stratakis CA.

Eur J Hum Genet. 2008 Jan;16(1):79-88. Epub 2007 Aug 1.

PubMed [citation]
PMID:
17667967

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, SCV000762660.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Leu20Cysfs*66) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587776649, ExAC 0.001%). This variant has been reported in an individual affected with gastrointestinal stromal tumor, pheochromocytoma, and multiple paragangliomas (PMID: 17667967). ClinVar contains an entry for this variant (Variation ID: 6917). 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: Dec 2, 2021

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