NM_004168.4(SDHA):c.554dup (p.Ala186fs) AND multiple conditions

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 2022
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:: RCV001384161.4

Allele description

NM_004168.4(SDHA):c.554dup (p.Ala186fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_004168.4(SDHA):c.554dup (p.Ala186fs)

HGVS:

NC_000005.10:g.225980dup
NG_012339.1:g.12740dup
NM_001294332.2:c.410dup
NM_001330758.2:c.554dup
NM_004168.4:c.554dupMANE SELECT
NP_001281261.1:p.Ala138fs
NP_001317687.1:p.Ala186fs
NP_004159.2:p.Ala186fs
LRG_315t1:c.554dup
LRG_315:g.12740dup
LRG_315p1:p.Ala186fs
NC_000005.9:g.226094_226095insA
NC_000005.9:g.226095dup
NM_004168.2:c.554dupA

Protein change:

A138fs

Links:

dbSNP: rs1173940446

NCBI 1000 Genomes Browser:

rs1173940446

Molecular consequence:

NM_001294332.2:c.410dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330758.2:c.554dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004168.4:c.554dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001583546	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22974104, 24781757, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583546

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 2022)

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

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 (3)

Details of each submission

From Invitae, SCV001583546.4

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1071644). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala186Glyfs*9) 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).

#	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: May 7, 2024

ClinVar

Relating variation to medicine