NM_003000.2(SDHB):c.717dup (p.Leu240fs) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jul 6, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000475105.3

Allele description [Variation Report for NM_003000.2(SDHB):c.717dup (p.Leu240fs)]

NM_003000.2(SDHB):c.717dup (p.Leu240fs)

Gene:
SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
1p36.13
Genomic location:
Preferred name:
NM_003000.2(SDHB):c.717dup (p.Leu240fs)
HGVS:
  • NC_000001.11:g.17022656dup
  • NG_012340.1:g.36515dup
  • NM_003000.2:c.717dup
  • NP_002991.2:p.Leu240fs
  • LRG_316t1:c.717dup
  • LRG_316:g.36515dup
  • LRG_316p1:p.Leu240fs
  • NC_000001.10:g.17349151dup
  • NM_003000.2:c.717dupT
Protein change:
L240fs
Links:
dbSNP: rs1060503764
NCBI 1000 Genomes Browser:
rs1060503764
Molecular consequence:
  • NM_003000.2:c.717dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Gastrointestinal stromal tumor (GIST)
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 4 (PGL4)
Synonyms:
CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Pheochromocytoma, extraadrenal and cervical paraganglioma; Paragangliomas, hereditary extraadrenal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310
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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000554018Invitaecriteria provided, single submitter
Pathogenic
(Jul 6, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000554018.3

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

Description

This sequence change results in a premature translational stop signal in the SDHB gene (p.Leu240Serfs*16). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acids of the SDHB protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 412481). A different truncation (deletion of exon 8) that lies downstream of this variant has been determined to be pathogenic (Invitae). This suggests that deletion of this region of the SDHB protein is causative of disease. 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

Support Center