NM_003000.3(SDHB):c.166_170del (p.Pro56fs) AND Pheochromocytoma

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 4, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001294007.3

Allele description [Variation Report for NM_003000.3(SDHB):c.166_170del (p.Pro56fs)]

NM_003000.3(SDHB):c.166_170del (p.Pro56fs)

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.166_170del (p.Pro56fs)

HGVS:

NC_000001.10:g.17371286_17371290del
NC_000001.11:g.17044792_17044796del
NG_012340.1:g.14376_14380del
NM_003000.3:c.166_170delMANE SELECT
NP_002991.2:p.Pro56fs
NP_002991.2:p.Pro56fs
LRG_316t1:c.166_170del
LRG_316:g.14376_14380del
LRG_316p1:p.Pro56fs
NC_000001.10:g.17371286_17371290del
NC_000001.10:g.17371287_17371291del
NC_000001.10:g.17371287_17371291delGAGGT
NM_003000.2:c.166_170del
NM_003000.2:c.166_170delCCTCA
p.P56YFS*5

Protein change:

P56fs

Links:

dbSNP: rs786202100

NCBI 1000 Genomes Browser:

rs786202100

Molecular consequence:

NM_003000.3:c.166_170del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001482758	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 7, 2018)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15328326, 21934479, 25130709, 28152038, 25741868
SCV002074521	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 4, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15328326, 19454582, 19258401, 30201732, 29386252 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001482758

Baylor Genetics - CSER-TexasKidsCanSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 7, 2018)

unknown

clinical testing

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

SCV002074521

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 4, 2022)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Renal tumors associated with germline SDHB mutation show distinctive morphology.

Gill AJ, Pachter NS, Chou A, Young B, Clarkson A, Tucker KM, Winship IM, Earls P, Benn DE, Robinson BG, Fleming S, Clifton-Bligh RJ.

Am J Surg Pathol. 2011 Oct;35(10):1578-85. doi: 10.1097/PAS.0b013e318227e7f4.

PubMed [citation]

PMID:: 21934479

Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report.

Jové M, Mora J, Sanjuan X, Rodriguez E, Robledo M, Farran L, Garcia del Muro X.

Histopathology. 2014 Nov;65(5):712-7. doi: 10.1111/his.12506. No abstract available.

PubMed [citation]

PMID:: 25130709

See all PubMed Citations (9)

Details of each submission

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV001482758.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 15328326, 21934479, 25130709, 28152038]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074521.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: SDHB c.166_170delCCTCA (p.Pro56TyrfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is also known as c.32_36delCCTCA in HGVS and 300-4delCCTCA in the literature. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251378 control chromosomes (gnomAD). c.166_170delCCTCA has been reported in the literature in multiple individuals affected with Paraganglioma and/or Pheochromocytoma (examples: Neumann_2004, Cascon_2009, Burnichon_2009, Andrews_2018 and Benn_2018). These data indicate that the variant is associated with disease. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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