NM_003000.3(SDHB):c.464C>T (p.Pro155Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 9, 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:: RCV000633952.5

Allele description [Variation Report for NM_003000.3(SDHB):c.464C>T (p.Pro155Leu)]

NM_003000.3(SDHB):c.464C>T (p.Pro155Leu)

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.464C>T (p.Pro155Leu)

HGVS:

NC_000001.11:g.17027825G>A
NG_012340.1:g.31346C>T
NM_003000.3:c.464C>TMANE SELECT
NP_002991.2:p.Pro155Leu
NP_002991.2:p.Pro155Leu
LRG_316t1:c.464C>T
LRG_316:g.31346C>T
LRG_316p1:p.Pro155Leu
NC_000001.10:g.17354320G>A
NM_003000.2:c.464C>T

Protein change:

P155L

Links:

dbSNP: rs1553177686

NCBI 1000 Genomes Browser:

rs1553177686

Molecular consequence:

NM_003000.3:c.464C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

Name:: Paragangliomas 4 (PPGL4)
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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000755225	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22517557, 34906457, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000755225

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 9, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma.

Buffet A, Venisse A, Nau V, Roncellin I, Boccio V, Le Pottier N, Boussion M, Travers C, Simian C, Burnichon N, Abermil N, Favier J, Jeunemaitre X, Gimenez-Roqueplo AP.

Horm Metab Res. 2012 May;44(5):359-66. doi: 10.1055/s-0032-1304594. Epub 2012 Apr 19. Review.

PubMed [citation]

PMID:: 22517557

Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.

Garrett A, Loveday C, King L, Butler S, Robinson R, Horton C, Yussuf A, Choi S, Torr B, Durkie M, Burghel GJ, Drummond J, Berry I, Wallace A, Callaway A, Eccles D, Tischkowitz M, Tatton-Brown K, Snape K, McVeigh T, Izatt L, Woodward ER, et al.

Genet Med. 2022 Jan;24(1):41-50. doi: 10.1016/j.gim.2021.08.004. Epub 2021 Nov 30.

PubMed [citation]

PMID:: 34906457
PMCID:: PMC8759765

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000755225.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function. ClinVar contains an entry for this variant (Variation ID: 528729). This missense change has been observed in individual(s) with pheochromocytoma and/or paraganglioma (PMID: 22517557, 34906457). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 155 of the SDHB protein (p.Pro155Leu).

#	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: Apr 15, 2024

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