NM_004168.4(SDHA):c.1237A>C (p.Ile413Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 20, 2023
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:: RCV003801714.2

Allele description [Variation Report for NM_004168.4(SDHA):c.1237A>C (p.Ile413Leu)]

NM_004168.4(SDHA):c.1237A>C (p.Ile413Leu)

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.1237A>C (p.Ile413Leu)

HGVS:

NC_000005.10:g.235316A>C
NG_012339.1:g.22076A>C
NM_001294332.2:c.1093A>C
NM_001330758.2:c.1237A>C
NM_004168.2:c.1237A>C
NM_004168.4:c.1237A>CMANE SELECT
NP_001281261.1:p.Ile365Leu
NP_001317687.1:p.Ile413Leu
NP_004159.2:p.Ile413Leu
LRG_315t1:c.1237A>C
LRG_315:g.22076A>C
LRG_315p1:p.Ile413Leu
NC_000005.9:g.235431A>C

Protein change:

I365L

Molecular consequence:

NM_001294332.2:c.1093A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330758.2:c.1237A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004168.4:c.1237A>C - 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

Name:: Paragangliomas 5 (PPGL5)
Synonyms:: PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 5
Identifiers:: MONDO: MONDO:0013602; MedGen: C3279992; Orphanet: 29072; OMIM: 614165

Recent activity

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Mus musculus syntaxin binding protein 6 (amisyn) (Stxbp6), transcript variant 4,...
Mus musculus syntaxin binding protein 6 (amisyn) (Stxbp6), transcript variant 4, mRNA
gi|2289229149|ref|NM_001411383.1|

Nucleotide
syntaxin-binding protein 6 isoform 1 [Mus musculus]
syntaxin-binding protein 6 isoform 1 [Mus musculus]
gi|2289229095|ref|NP_001398310.1|

Protein
beta-arrestin-2 isoform X2 [Mus musculus]
beta-arrestin-2 isoform X2 [Mus musculus]
gi|1907081169|ref|XP_036012467.1|

Protein
syntaxin-binding protein 6 isoform X1 [Mus musculus]
syntaxin-binding protein 6 isoform X1 [Mus musculus]
gi|1907086810|ref|XP_036013201.1|

Protein
nitric oxide-associated protein 1 isoform 5 [Mus musculus]
nitric oxide-associated protein 1 isoform 5 [Mus musculus]
gi|2711571101|ref|NP_001415967.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004596392	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004596392

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 20, 2023)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004596392.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 413 of the SDHA protein (p.Ile413Leu). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHA protein function. 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).

#	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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