ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.650C>T (p.Thr217Ile)

gnomAD frequency: 0.00009  dbSNP: rs144631139
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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 RCV002537833 SCV003508455 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2022-05-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 217 of the MCCC2 protein (p.Thr217Ile). This variant is present in population databases (rs144631139, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 991031). 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. 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.
Natera, Inc. RCV001279168 SCV001466250 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-08-31 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004751946 SCV005350399 uncertain significance MCCC2-related disorder 2024-07-19 no assertion criteria provided clinical testing The MCCC2 c.650C>T variant is predicted to result in the amino acid substitution p.Thr217Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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