ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1488G>C (p.Gln496His)

gnomAD frequency: 0.00001  dbSNP: rs745367639
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001364598 SCV001560755 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 496 of the MCCC2 protein (p.Gln496His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant also falls at the last nucleotide of exon 15, which is part of the consensus splice site for this exon. This variant is present in population databases (rs745367639, ExAC 0.03%). This missense change has been observed in individual(s) with methylcrotonylglycinuria (PMID: 22030835). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Baylor Genetics RCV001364598 SCV004194386 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-02-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV001364598 SCV002084923 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2020-06-21 no assertion criteria provided clinical testing

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