NM_003000.3(SDHB):c.3G>A (p.Met1Ile) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 2021
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:: RCV001379744.6

Allele description [Variation Report for NM_003000.3(SDHB):c.3G>A (p.Met1Ile)]

NM_003000.3(SDHB):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)

HGVS:

NC_000001.11:g.17054017C>T
NG_012340.1:g.5154G>A
NM_003000.3:c.3G>AMANE SELECT
NP_002991.2:p.Met1Ile
NP_002991.2:p.Met1Ile
LRG_316t1:c.3G>A
LRG_316:g.5154G>A
LRG_316p1:p.Met1Ile
NC_000001.10:g.17380512C>T
NM_003000.2:c.3G>A

Protein change:

M1I

Links:

dbSNP: rs1131691061

NCBI 1000 Genomes Browser:

rs1131691061

Molecular consequence:

NM_003000.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_003000.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: 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:: Pheochromocytoma/paraganglioma syndrome 4
Synonyms:: CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; PARAGANGLIOMA, FAMILIAL MALIGNANT; PARAGANGLIOMAS, HEREDITARY EXTRAADRENAL; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310

Name:: Pheochromocytoma
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
SCV001577603	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2021)	germline	clinical testing	PubMed (18) [See all records that cite these PMIDs] 19351833, 22241717, 23407919, 23512077, 24096523, 25047027, 27279923, 28490599, 29951630, 12618761, 14500403, 15328326, 16314641, 17102082, 18362451, 23083876, 23282968, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001577603

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2021)

germline

clinical testing

PubMed (18)
[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

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

Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients.

Piccini V, Rapizzi E, Bacca A, Di Trapani G, Pulli R, Giachè V, Zampetti B, Lucci-Cordisco E, Canu L, Corsini E, Faggiano A, Deiana L, Carrara D, Tantardini V, Mariotti S, Ambrosio MR, Zatelli MC, Parenti G, Colao A, Pratesi C, Bernini G, Ercolino T, et al.

Endocr Relat Cancer. 2012 Apr 10;19(2):149-55. doi: 10.1530/ERC-11-0369. Print 2012 Apr.

PubMed [citation]

PMID:: 22241717

See all PubMed Citations (18)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001577603.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)

Description

This sequence change affects the initiator methionine of the SDHB mRNA. The next in-frame methionine is located at codon 58. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator codon has been observed in individuals with paragangliomas, pheochromocytomas and renal cell carcinomas (PMID: 19351833, 22241717, 23407919, 23512077, 24096523, 25047027, 27279923, 28490599, 29951630). ClinVar contains an entry for this variant (Variation ID: 428932). This variant disrupts the p.Arg46 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12618761, 14500403, 15328326, 16314641, 17102082, 18362451, 23083876, 23282968). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been 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: Nov 15, 2025

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