ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.295G>C (p.Glu99Gln) (rs119103219)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082095 SCV000230396 pathogenic not provided 2015-01-06 criteria provided, single submitter clinical testing
GeneDx RCV000082095 SCV000321869 pathogenic not provided 2018-07-18 criteria provided, single submitter clinical testing The E99Q missense variant in the MCCC2 gene has been reported previously in association with3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Baumgartner et al., 2001; Grunert et al.,2012). In-vitro expression studies found that E99Q is associated with no detectable 3-MCC enzymeactivity (Baumgartner et al., 2001). The E99Q variant is not observed at a significant frequency inlarge population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). In summary, we interpret E99Q to be a pathogenic variant.
Invitae RCV000001997 SCV000956008 pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 99 of the MCCC2 protein (p.Glu99Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs119103219, ExAC 0.004%). This variant has been observed to be homozygous or in combination with another MCCC2 variant in an several individuals affected with 3-Methylcrotonyl-CoA carboxylase deficiency (PMID: 11181649, 22642865, 11406611). ClinVar contains an entry for this variant (Variation ID: 1920). Experimental studies have shown that this missense change abrogates MCCC2 protein enzymatic activity (PMID: 11181649). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001997 SCV000022155 pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2001-02-01 no assertion criteria provided literature only

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