NM_003850.3(SUCLA2):c.629T>C (p.Ile210Thr) AND Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 2022
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:: RCV001337610.5

Allele description [Variation Report for NM_003850.3(SUCLA2):c.629T>C (p.Ile210Thr)]

NM_003850.3(SUCLA2):c.629T>C (p.Ile210Thr)

Gene:

SUCLA2:succinate-CoA ligase ADP-forming subunit beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_003850.3(SUCLA2):c.629T>C (p.Ile210Thr)

Other names:

p.Ile210Thr

HGVS:

NC_000013.11:g.47973298A>G
NG_008241.1:g.33030T>C
NM_003850.2:c.629T>C
NM_003850.3:c.629T>CMANE SELECT
NP_003841.1:p.Ile210Thr
NC_000013.10:g.48547433A>G

Protein change:

I210T

Links:

dbSNP: rs773355734

NCBI 1000 Genomes Browser:

rs773355734

Molecular consequence:

NM_003850.3:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MTDPS5)
Synonyms:: Encephalomyopathy; Mitochondrial encephalomyopathy aminoacidopathy; MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC FORM, WITH OR WITHOUT METHYLMALONIC ACIDURIA, AUTOSOMAL RECESSIVE, SUCLA2-RELATED; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012791; MedGen: C2749864; Orphanet: 1933; OMIM: 612073

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001531217	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2022)	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

SCV001531217

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2022)

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, SCV001531217.4

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

Description

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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SUCLA2 protein function. ClinVar contains an entry for this variant (Variation ID: 1034831). This variant has not been reported in the literature in individuals affected with SUCLA2-related conditions. This variant is present in population databases (rs773355734, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 210 of the SUCLA2 protein (p.Ile210Thr).

#	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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