NM_003000.3(SDHB):c.143A>T (p.Asp48Val) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 2024
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:: RCV000470589.12

Allele description

NM_003000.3(SDHB):c.143A>T (p.Asp48Val)

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.143A>T (p.Asp48Val)

HGVS:

NC_000001.11:g.17044818T>A
NG_012340.1:g.14353A>T
NM_003000.3:c.143A>TMANE SELECT
NP_002991.2:p.Asp48Val
NP_002991.2:p.Asp48Val
LRG_316t1:c.143A>T
LRG_316:g.14353A>T
LRG_316p1:p.Asp48Val
NC_000001.10:g.17371313T>A
NM_003000.2:c.143A>T

Protein change:

D48V; ASP48VAL

Links:

OMIM: 185470.0020; dbSNP: rs202101384

NCBI 1000 Genomes Browser:

rs202101384

Molecular consequence:

NM_003000.3:c.143A>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
SCV000553986	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26642834, 26925370, 27604842, 22972948, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000553986

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

PubMed (5)
[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

Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.

Helman G, Caldovic L, Whitehead MT, Simons C, Brockmann K, Edvardson S, Bai R, Moroni I, Taylor JM, Van Haren K; SDH Study Group., Taft RJ, Vanderver A, van der Knaap MS.

Ann Neurol. 2016 Mar;79(3):379-86. doi: 10.1002/ana.24572. Epub 2016 Feb 12. Erratum in: Ann Neurol. 2018 Sep;84(3):481. doi: 10.1002/ana.25296.

PubMed [citation]

PMID:: 26642834
PMCID:: PMC5712845

Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.

Ardissone A, Invernizzi F, Nasca A, Moroni I, Farina L, Ghezzi D.

Mol Genet Metab Rep. 2015 Dec;5:51-54.

PubMed [citation]

PMID:: 26925370
PMCID:: PMC4695914

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000553986.9

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 48 of the SDHB protein (p.Asp48Val). This variant is present in population databases (rs202101384, gnomAD 0.03%). This missense change has been observed in individual(s) with autosomal recessive mitochondrial complex II deficiency (PMID: 22972948, 26642834, 26925370, 27604842). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 39584). 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 not expected to disrupt SDHB protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects SDHB function (PMID: 22972948). 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: Sep 16, 2024

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