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NM_003000.3(SDHB):c.801del (p.Lys268_Met269insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 11, 2017
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:
RCV002419263.2

Allele description [Variation Report for NM_003000.3(SDHB):c.801del (p.Lys268_Met269insTer)]

NM_003000.3(SDHB):c.801del (p.Lys268_Met269insTer)

Gene:
SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p36.13
Genomic location:
Preferred name:
NM_003000.3(SDHB):c.801del (p.Lys268_Met269insTer)
HGVS:
  • NC_000001.11:g.17018923del
  • NG_012340.1:g.40248del
  • NM_001407361.1:c.747delG
  • NM_003000.3:c.801delMANE SELECT
  • NP_001394290.1:p.Met251Terfs
  • NP_002991.2:p.Lys268_Met269insTer
  • NP_002991.2:p.Met269Terfs
  • LRG_316t1:c.801del
  • LRG_316:g.40248del
  • LRG_316p1:p.Met269Terfs
  • NC_000001.10:g.17345418del
  • NM_003000.2:c.801delG
Molecular consequence:
  • NM_001407361.1:c.747delG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003000.3:c.801del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407361.1:c.747delG - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002680905Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Dec 11, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, et al.

Cancer Res. 2009 Apr 15;69(8):3650-6. doi: 10.1158/0008-5472.CAN-08-4057. Epub 2009 Apr 7.

PubMed [citation]
PMID:
19351833

A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma.

Rattenberry E, Vialard L, Yeung A, Bair H, McKay K, Jafri M, Canham N, Cole TR, Denes J, Hodgson SV, Irving R, Izatt L, Korbonits M, Kumar AV, Lalloo F, Morrison PJ, Woodward ER, Macdonald F, Wallis Y, Maher ER.

J Clin Endocrinol Metab. 2013 Jul;98(7):E1248-56. doi: 10.1210/jc.2013-1319. Epub 2013 May 10.

PubMed [citation]
PMID:
23666964

Details of each submission

From Ambry Genetics, SCV002680905.2

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

Description

The c.801delG variant (also known as p.M269*), located in coding exon 8 of the SDHB gene, results from a deletion of one nucleotide at position 801. This changes the amino acid from a methionine to a stop codon within coding exon 8. This stop codon occurs at the 3' terminus of SDHB, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 11 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time; however, this variant has been identified in at least one individual with a paraganglioma and/or pheochromocytoma (Ambry internal data). In addition, several other variants with predicted premature termination codons near the C-terminus have been identified in patients affected with paraganglioma or pheochromocytomas including SDHB c.784_787dupGCTA (p.I263fs*13), SDHB c.780delG (p.A262Lfs*8), and SDHB c.770dupT (p.N258Efs*17) (Ambry internal data; Neumann HP et al. Cancer Res. 2009 Apr;69:3650-6; Rattenberry E et al. J. Clin. Endocrinol. Metab. 2013 Jul;98:E1248-56). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: May 1, 2024