ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1315G>A (p.Val439Met)

gnomAD frequency: 0.00001  dbSNP: rs398124352
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000259066 SCV000113926 uncertain significance not provided 2015-04-27 criteria provided, single submitter clinical testing
Invitae RCV000653496 SCV000775376 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 439 of the MCCC1 protein (p.Val439Met). This variant is present in population databases (rs398124352, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865, 31901042; Invitae). ClinVar contains an entry for this variant (Variation ID: 95940). 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 MCCC1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003398679 SCV004104077 uncertain significance MCCC1-related condition 2023-03-15 criteria provided, single submitter clinical testing The MCCC1 c.1315G>A variant is predicted to result in the amino acid substitution p.Val439Met. This variant has been reported in a compound heterozygous and a homozygous unrelated individual with 3-methylcrotonyl-CoA carboxylase deficiency (Grünert et al 2012. PubMed ID: 22642865; Wu D et al 2019. PubMed ID: 31901042). This variant is reported in 0.0028% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-182756876-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV000653496 SCV004194261 likely pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-09-09 criteria provided, single submitter clinical testing
Natera, Inc. RCV000653496 SCV002079098 likely pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2020-12-23 no assertion criteria provided clinical testing

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