ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.137G>A (p.Gly46Glu) (rs199517715)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000185992 SCV000281549 pathogenic not provided 2015-10-09 criteria provided, single submitter clinical testing
Invitae RCV000554762 SCV000656953 uncertain significance 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2019-08-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 46 of the MCCC1 protein (p.Gly46Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs199517715, ExAC 0.01%). This variant has been reported in combination with another MCCC1 variant in an individual affected with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 21071250). ClinVar contains an entry for this variant (Variation ID: 203797). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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