NM_004168.4(SDHA):c.1283_1298del (p.Gln428fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 27, 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:: RCV003097776.2

Allele description [Variation Report for NM_004168.4(SDHA):c.1283_1298del (p.Gln428fs)]

NM_004168.4(SDHA):c.1283_1298del (p.Gln428fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_004168.4(SDHA):c.1283_1298del (p.Gln428fs)

HGVS:

NC_000005.10:g.236450_236465del
NG_012339.1:g.23210_23225del
NM_001294332.2:c.1139_1154del
NM_001330758.2:c.1283_1298del
NM_004168.4:c.1283_1298delMANE SELECT
NP_001281261.1:p.Gln380fs
NP_001317687.1:p.Gln428fs
NP_004159.2:p.Gln428fs
LRG_315t1:c.1283_1298del
LRG_315:g.23210_23225del
LRG_315p1:p.Gln428fs
NC_000005.9:g.236562_236577del
NC_000005.9:g.236565_236580del
NM_004168.2:c.1283_1298del16

Protein change:

Q380fs

Molecular consequence:

NM_001294332.2:c.1139_1154del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330758.2:c.1283_1298del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004168.4:c.1283_1298del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003459951	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 27, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28384794, 22974104, 24781757, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003459951

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 27, 2021)

germline

clinical testing

PubMed (4)
[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 Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

Bausch B, Schiavi F, Ni Y, Welander J, Patocs A, Ngeow J, Wellner U, Malinoc A, Taschin E, Barbon G, Lanza V, Söderkvist P, Stenman A, Larsson C, Svahn F, Chen JL, Marquard J, Fraenkel M, Walter MA, Peczkowska M, Prejbisz A, Jarzab B, et al.

JAMA Oncol. 2017 Sep 1;3(9):1204-1212. doi: 10.1001/jamaoncol.2017.0223.

PubMed [citation]

PMID:: 28384794
PMCID:: PMC5824290

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 (4)

Details of each submission

From Invitae, SCV003459951.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndromes (PMID: 28384794). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln428Profs*37) 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

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