ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.499T>C (p.Cys167Arg)

gnomAD frequency: 0.00001  dbSNP: rs119103222
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000002000 SCV000458145 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2016-07-28 criteria provided, single submitter clinical testing The MCCC2 c.499T>C (p.Cys167Arg) variant is a missense variant that has been reported in a homozygous state in one individual with 3-methylcrotonyl-CoA carboxylase deficiency (Gallardo et al. 2001). The p.Cys167Arg variant was absent from 100 controls. It is reported at a frequency of 0.00009 in the Latino population of the Exome Aggregation Consortium, but this frequency is based on one allele in a region of good sequence coverage; therefore, the variant is presumed to be rare. Based on the limited evidence, the p.Cys167Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for 3-methylcrotonyl-CoA carboxylase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000002000 SCV000961815 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-05-01 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with autosomal recessive 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 11170888, 14680978). This variant is present in population databases (rs119103222, gnomAD 0.006%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 167 of the MCCC2 protein (p.Cys167Arg). ClinVar contains an entry for this variant (Variation ID: 1923). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MCCC2 function (PMID: 14680978). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MCCC2 protein function.
Baylor Genetics RCV000002000 SCV004194316 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-10-25 criteria provided, single submitter clinical testing
OMIM RCV000002000 SCV000022158 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2001-02-01 no assertion criteria provided literature only
Natera, Inc. RCV000002000 SCV002084288 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2020-12-24 no assertion criteria provided clinical testing

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