NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 28, 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:: RCV000684799.10

Allele description [Variation Report for NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)]

NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)

Gene:

SDHA:succinate dehydrogenase complex flavoprotein subunit A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)

Other names:

p.Arg512*

HGVS:

NC_000005.10:g.240459C>T
NG_012339.1:g.27219C>T
NM_001294332.2:c.1390C>T
NM_001330758.2:c.1534C>T
NM_004168.4:c.1534C>TMANE SELECT
NP_001281261.1:p.Arg464Ter
NP_001317687.1:p.Arg512Ter
NP_004159.2:p.Arg512Ter
LRG_315t1:c.1534C>T
LRG_315:g.27219C>T
LRG_315p1:p.Arg512Ter
NC_000005.9:g.240574C>T
NM_004168.2:c.1534C>T
NM_004168.3:c.1534C>T

Protein change:

R464*

Links:

dbSNP: rs748089700

NCBI 1000 Genomes Browser:

rs748089700

Molecular consequence:

NM_001294332.2:c.1390C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001330758.2:c.1534C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004168.4:c.1534C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Mitochondrial complex II deficiency, nuclear type 1
Synonyms:: Mitochondrial complex II deficiency; Complex 2 mitochondrial respiratory chain deficiency; Succinate CoQ reductase deficiency
Identifiers:: MONDO: MONDO:0100294; MedGen: C5700310; Orphanet: 3208; OMIM: 252011

Name:: Paragangliomas 5 (PPGL5)
Synonyms:: PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 5
Identifiers:: MONDO: MONDO:0013602; MedGen: C3279992; Orphanet: 29072; OMIM: 614165

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000553882	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 28, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22974104, 24781757, 22955521, 25720320, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000553882

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 28, 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

SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors.

Italiano A, Chen CL, Sung YS, Singer S, DeMatteo RP, LaQuaglia MP, Besmer P, Socci N, Antonescu CR.

BMC Cancer. 2012 Sep 14;12:408. doi: 10.1186/1471-2407-12-408.

PubMed [citation]

PMID:: 22974104
PMCID:: PMC3503624

SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors.

Renkema GH, Wortmann SB, Smeets RJ, Venselaar H, Antoine M, Visser G, Ben-Omran T, van den Heuvel LP, Timmers HJ, Smeitink JA, Rodenburg RJ.

Eur J Hum Genet. 2015 Feb;23(2):202-9. doi: 10.1038/ejhg.2014.80. Epub 2014 Apr 30.

PubMed [citation]

PMID:: 24781757
PMCID:: PMC4297908

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000553882.9

#	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 creates a premature translational stop signal (p.Arg512*) in the SDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). This variant is present in population databases (rs748089700, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with paraganglioma and/or gastrointestinal stromal tumor (PMID: 22955521, 25720320). ClinVar contains an entry for this variant (Variation ID: 371805). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 29, 2024

ClinVar

Relating variation to medicine