ClinVar Miner

Submissions for variant NM_001258392.3(CLPB):c.1591C>T (p.Arg531Trp)

dbSNP: rs1949512456
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kids Research, The Children's Hospital at Westmead RCV001089495 SCV001244740 uncertain significance 3-methylglutaconic aciduria, type VIIB criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001089495 SCV002145867 pathogenic 3-methylglutaconic aciduria, type VIIB 2022-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 561 of the CLPB protein (p.Arg561Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neutropenia and neurodevelopmental syndrome (PMID: 32313153, 34140661; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 869400). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
3billion RCV002283523 SCV002572732 pathogenic 3-methylglutaconic aciduria, type VIIA 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.82; 3Cnet: 0.59). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CLPB-related disorder (PMID: 34140661). The variant has been previously reported as de novo in at least two similarly affected unrelated individuals, and observed in at least two similarly affected unrelated individuals (PMID: 34140661). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity RCV003145344 SCV003831041 uncertain significance not provided 2021-04-05 criteria provided, single submitter clinical testing
OMIM RCV001089495 SCV002499265 pathogenic 3-methylglutaconic aciduria, type VIIB 2022-08-11 no assertion criteria provided literature only

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