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NM_003000.3(SDHB):c.680del (p.Thr227fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 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:
RCV003377773.2

Allele description [Variation Report for NM_003000.3(SDHB):c.680del (p.Thr227fs)]

NM_003000.3(SDHB):c.680del (p.Thr227fs)

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.680del (p.Thr227fs)
HGVS:
  • NC_000001.11:g.17022693del
  • NG_012340.1:g.36478del
  • NM_001407361.1:c.626del
  • NM_003000.3:c.680delMANE SELECT
  • NP_001394290.1:p.Thr209fs
  • NP_002991.2:p.Thr227Lysfs
  • NP_002991.2:p.Thr227fs
  • LRG_316t1:c.680del
  • LRG_316:g.36478del
  • LRG_316p1:p.Thr227Lysfs
  • NC_000001.10:g.17349188del
  • NM_003000.2:c.680delC
Protein change:
T209fs
Molecular consequence:
  • NM_001407361.1:c.626del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003000.3:c.680del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004097197Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 5, 2023) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV004097197.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.680delC pathogenic mutation, located in coding exon 7 of the SDHB gene, results from a deletion of one nucleotide at nucleotide position 680, causing a translational frameshift with a predicted alternate stop codon (p.T227Kfs*21). This alteration occurs at the 3' terminus of theSDHB gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 54 amino acids of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHB-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 1, 2024