ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1635dup (p.Ser546Ter)

dbSNP: rs768272570
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644019 SCV000765706 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser546*) in the MCCC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the MCCC2 protein. This variant is present in population databases (rs768272570, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for MCCC2-related disease (PMID: 27601257; internal data). ClinVar contains an entry for this variant (Variation ID: 535825). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the MCCC2 protein in which other variant(s) (p.Thr556Ile) have been determined to be pathogenic (PMID: 25381946; internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000644019 SCV002782549 uncertain significance 3-methylcrotonyl-CoA carboxylase 2 deficiency 2021-08-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV000644019 SCV004194360 likely pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-07-09 criteria provided, single submitter clinical testing
GeneDx RCV004719914 SCV005325927 likely pathogenic not provided 2023-10-30 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation, as the last 18 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35281663, 27601257)
Natera, Inc. RCV001271414 SCV001452540 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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