NM_004168.4(SDHA):c.1523C>T (p.Thr508Ile) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Oct 1, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001719715.24

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]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000714403	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Oct 27, 2020)	germline	clinical testing	Citation Link,
SCV002821281	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Oct 1, 2023)	germline	clinical testing	Citation Link,
SCV004227052	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 23, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22972948, 26642834, 28724664, 29778030, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000714403

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Oct 27, 2020)

germline

clinical testing

Citation Link,

SCV002821281

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely benign
(Oct 1, 2023)

germline

clinical testing

Citation Link,

SCV004227052

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 23, 2023)

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	10	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	3	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

Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.

Helman G, Caldovic L, Whitehead MT, Simons C, Brockmann K, Edvardson S, Bai R, Moroni I, Taylor JM, Van Haren K; SDH Study Group., Taft RJ, Vanderver A, van der Knaap MS.

Ann Neurol. 2016 Mar;79(3):379-86. doi: 10.1002/ana.24572. Epub 2016 Feb 12. Erratum in: Ann Neurol. 2018 Sep;84(3):481. doi: 10.1002/ana.25296.

PubMed [citation]

PMID:: 26642834
PMCID:: PMC5712845

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000714403.3

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

Description

This variant is associated with the following publications: (PMID: 22972948, 26642834, 23174333, 28724664, 29778030)

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

From CeGaT Center for Human Genetics Tuebingen, SCV002821281.14

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

Description

SDHA: PP3, BS1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV004227052.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	clinical testing	PubMed (5)

#	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		10	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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