ClinVar Miner

Submissions for variant NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly) (rs144078282)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000167542 SCV000265562 pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2015-09-04 criteria provided, single submitter research
GeneDx RCV000487136 SCV000568867 pathogenic not provided 2020-08-31 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with R408G resulting in little to no residual enzyme activity (Wortmann et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25597510, 27290639, 28554332, 28687938, 27891836)
Invitae RCV000167542 SCV000823538 pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2020-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 408 of the CLPB protein (p.Arg408Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs144078282, ExAC 0.03%). This variant has been reported to segregate with 3-methylglutaconic aciduria in a family (PMID: 25597510). It has also been reported in several unrelated affected individuals (PMID: 28554332, 27290639, 28687938). ClinVar contains an entry for this variant (Variation ID: 187785). Experimental studies have shown that this missense change disrupts CLPB enzymatic activity in vitro (PMID: 25597510). For these reasons, this variant has been classified as Pathogenic.
SIB Swiss Institute of Bioinformatics RCV000167542 SCV000883174 likely pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Likely Pathogenic, for 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/25597510).
Baylor Genetics RCV000167542 SCV001521676 likely pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2019-09-30 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
OMIM RCV000167542 SCV000218400 pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2015-02-05 no assertion criteria provided literature only
GeneReviews RCV000167542 SCV000328964 pathogenic 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 2016-09-14 no assertion criteria provided literature only
Human Genetics - Radboudumc,Radboudumc RCV000487136 SCV001959441 pathogenic not provided no assertion criteria provided clinical testing

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