NM_213720.3(CHCHD10):c.43C>T (p.Arg15Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 2, 2024
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:: RCV002572099.2

Allele description [Variation Report for NM_213720.3(CHCHD10):c.43C>T (p.Arg15Cys)]

NM_213720.3(CHCHD10):c.43C>T (p.Arg15Cys)

Gene:

CHCHD10:coiled-coil-helix-coiled-coil-helix domain containing 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.23

Genomic location:

Preferred name:

NM_213720.3(CHCHD10):c.43C>T (p.Arg15Cys)

HGVS:

NC_000022.11:g.23767592G>A
NG_034223.1:g.5381C>T
NM_001301339.2:c.43C>T
NM_213720.3:c.43C>TMANE SELECT
NP_001288268.1:p.Arg15Cys
NP_998885.1:p.Arg15Cys
NC_000022.10:g.24109779G>A

Protein change:

R15C

Molecular consequence:

NM_001301339.2:c.43C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_213720.3:c.43C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lower motor neuron syndrome with late-adult onset (SMAJ)
Synonyms:: Spinal muscular atrophy, Jokela type
Identifiers:: MONDO: MONDO:0014025; MedGen: C3554398; Orphanet: 276435; OMIM: 615048

Name:: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2
Synonyms:: FTDALS2
Identifiers:: MONDO: MONDO:0014395; MedGen: C4014648; Orphanet: 275872; OMIM: 615911

Name:: Autosomal dominant mitochondrial myopathy with exercise intolerance (IMMD)
Synonyms:: Myopathy, isolated mitochondrial, autosomal dominant
Identifiers:: MONDO: MONDO:0014532; MedGen: C4015513; Orphanet: 457050; OMIM: 616209

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002938789	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25113787, 25261972, 25681414, 28585542, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002938789

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease.

Müller K, Andersen PM, Hübers A, Marroquin N, Volk AE, Danzer KM, Meitinger T, Ludolph AC, Strom TM, Weishaupt JH.

Brain. 2014 Dec;137(Pt 12):e309. doi: 10.1093/brain/awu227. Epub 2014 Aug 11. No abstract available.

PubMed [citation]

PMID:: 25113787

Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis.

Johnson JO, Glynn SM, Gibbs JR, Nalls MA, Sabatelli M, Restagno G, Drory VE, Chiò A, Rogaeva E, Traynor BJ.

Brain. 2014 Dec;137(Pt 12):e311. doi: 10.1093/brain/awu265. Epub 2014 Sep 26. No abstract available.

PubMed [citation]

PMID:: 25261972
PMCID:: PMC4240285

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002938789.2

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 15 of the CHCHD10 protein (p.Arg15Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHCHD10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1897589). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Arg15 amino acid residue in CHCHD10. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25113787, 25261972, 25681414, 28585542). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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: Mar 5, 2024

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