NM_004168.4(SDHA):c.1615dup (p.Ile539fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 4, 2016
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:: RCV000457642.5

Allele description [Variation Report for NM_004168.4(SDHA):c.1615dup (p.Ile539fs)]

NM_004168.4(SDHA):c.1615dup (p.Ile539fs)

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.1615dup (p.Ile539fs)

HGVS:

NC_000005.10:g.251055dup
NG_012339.1:g.37815dup
NM_001294332.2:c.1471dup
NM_001330758.2:c.1552-3338dup
NM_004168.4:c.1615dupMANE SELECT
NP_001281261.1:p.Ile491fs
NP_004159.2:p.Ile539fs
LRG_315t1:c.1615dup
LRG_315:g.37815dup
LRG_315p1:p.Ile539fs
NC_000005.9:g.251166_251167insA
NC_000005.9:g.251170dup
NM_004168.2:c.1615dupA

Protein change:

I491fs

Links:

dbSNP: rs1554001843

NCBI 1000 Genomes Browser:

rs1554001843

Molecular consequence:

NM_001294332.2:c.1471dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004168.4:c.1615dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330758.2:c.1552-3338dup - intron variant - [Sequence Ontology: SO:0001627]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000553881	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 4, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24781757, 22974104, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000553881

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 4, 2016)

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 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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000553881.5

#	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. While this particular variant has not been reported in the literature, truncating variants in SDHA are known to be pathogenic (PMID: 24781757, 22974104). This sequence change inserts 1 nucleotide in exon 12 of the SDHA mRNA (c.1615dupA), causing a frameshift at codon 539. This creates a premature translational stop signal (p.Ile539Asnfs*64) and is expected to result in an absent or disrupted protein product.

#	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

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