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NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 26, 2021
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:
RCV002516522.2

Allele description [Variation Report for NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)]

NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)

Genes:
CLPB:ClpB family mitochondrial disaggregase [Gene - OMIM - HGNC]
LOC126861258:MED14-independent group 3 enhancer GRCh37_chr11:72012242-72013441 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.4
Genomic location:
Preferred name:
NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)
HGVS:
  • NC_000011.10:g.72302339T>C
  • NG_042130.2:g.137346A>G
  • NM_001258392.3:c.1132A>GMANE SELECT
  • NM_001258393.3:c.1045A>G
  • NM_001258394.3:c.1087A>G
  • NM_030813.6:c.1222A>G
  • NP_001245321.1:p.Arg378Gly
  • NP_001245322.1:p.Arg349Gly
  • NP_001245323.1:p.Arg363Gly
  • NP_110440.1:p.Arg408Gly
  • LRG_1338t1:c.1132A>G
  • LRG_1338:g.137346A>G
  • LRG_1338p1:p.Arg378Gly
  • NC_000011.9:g.72013383T>C
  • NM_030813.3:c.1222A>G
  • NM_030813.4:c.1222A>G
  • NM_030813.5:c.1222A>G
  • Q9H078:p.Arg408Gly
Protein change:
R349G; ARG408GLY
Links:
UniProtKB: Q9H078#VAR_073399; OMIM: 616254.0006; dbSNP: rs144078282
NCBI 1000 Genomes Browser:
rs144078282
Molecular consequence:
  • NM_001258392.3:c.1132A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258393.3:c.1045A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258394.3:c.1087A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030813.6:c.1222A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003627328Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 26, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

Wortmann SB, Ziętkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lücke T, Õunap K, Zordania R, et al.

Am J Hum Genet. 2015 Feb 5;96(2):245-57. doi: 10.1016/j.ajhg.2014.12.013. Epub 2015 Jan 15.

PubMed [citation]
PMID:
25597510
PMCID:
PMC4320260

New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.

Pronicka E, Piekutowska-Abramczuk D, Ciara E, Trubicka J, Rokicki D, Karkucińska-Więckowska A, Pajdowska M, Jurkiewicz E, Halat P, Kosińska J, Pollak A, Rydzanicz M, Stawinski P, Pronicki M, Krajewska-Walasek M, Płoski R.

J Transl Med. 2016 Jun 12;14(1):174. doi: 10.1186/s12967-016-0930-9.

PubMed [citation]
PMID:
27290639
PMCID:
PMC4903158
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003627328.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.1222A>G (p.R408G) alteration is located in exon 11 (coding exon 11) of the CLPB gene. This alteration results from an A to G substitution at nucleotide position 1222, causing the arginine (R) at amino acid position 408 to be replaced by a glycine (G). Based on data from the Genome Aggregation Database (gnomAD) database, the CLPB c.1222A>G alteration was observed in 0.02% (58/282666) of total alleles studied, with a frequency of 0.04% (51/129018) in the European (non-Finnish) subpopulation. This alteration has been confirmed in trans with a second disease-causing allele in multiple individuals with 3-methylglutaconic aciduria, developmental delay/intellectual disability, microcephaly, neutropenia, and/or cataracts (Wortmann, 2015; Pronicka, 2016; Pronicka, 2017; Bowling, 2017). This amino acid position is highly conserved in available vertebrate species. In vitro analysis revealed this alteration leads to reduced ATPase activity as compared to wild-type protein (Wortmann, 2015). The in silico prediction for the p.R408G alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024