NM_004168.4(SDHA):c.1523C>T (p.Thr508Ile) AND Mitochondrial complex II deficiency, nuclear type 1

Germline classification:: Likely benign (2 submissions)
Last evaluated:: May 28, 2019
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:: RCV000032785.13

Allele description [Variation Report for NM_004168.4(SDHA):c.1523C>T (p.Thr508Ile)]

NM_004168.4(SDHA):c.1523C>T (p.Thr508Ile)

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.1523C>T (p.Thr508Ile)

Other names:

p.Thr508Ile

HGVS:

NC_000005.10:g.240448C>T
NG_012339.1:g.27208C>T
NM_001294332.2:c.1379C>T
NM_001330758.2:c.1523C>T
NM_004168.4:c.1523C>TMANE SELECT
NP_001281261.1:p.Thr460Ile
NP_001317687.1:p.Thr508Ile
NP_004159.2:p.Thr508Ile
LRG_315t1:c.1523C>T
LRG_315:g.27208C>T
LRG_315p1:p.Thr508Ile
NC_000005.9:g.240563C>T
NM_004168.2:c.1523C>T
NM_004168.3:c.1523C>T

Protein change:

T460I; THR508ILE

Links:

OMIM: 600857.0006; dbSNP: rs151266052

NCBI 1000 Genomes Browser:

rs151266052

Molecular consequence:

NM_001294332.2:c.1379C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330758.2:c.1523C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004168.4:c.1523C>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000056549	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001136799	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000056549

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2012)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001136799

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely benign
(May 28, 2019)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.

Alston CL, Davison JE, Meloni F, van der Westhuizen FH, He L, Hornig-Do HT, Peet AC, Gissen P, Goffrini P, Ferrero I, Wassmer E, McFarland R, Taylor RW.

J Med Genet. 2012 Sep;49(9):569-77. doi: 10.1136/jmedgenet-2012-101146.

PubMed [citation]

PMID:: 22972948
PMCID:: PMC3500770

Details of each submission

From OMIM, SCV000056549.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a boy with mitochondrial complex II deficiency nuclear type 1 (MC2DN1; 252011) manifest as cardiomyopathy and leukoencephalopathy, Alston et al. (2012) identified compound heterozygosity for 2 mutations in the SDHA gene: a 1523C-T transition in exon 11 resulting in a thr508-to-ile (T508I) substitution, and a 1526C-T transition in exon 11 resulting in a ser509-to-leu (S509L; 600857.0007) substitution. Both mutations occurred at highly conserved residues within the catalytic flavoprotein subunit of the complex. Each unaffected parent was heterozygous for 1 of the mutations.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV001136799.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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