ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.517dup (p.Ser173fs)

dbSNP: rs587776533
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000001996 SCV000644151 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2025-01-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser173Phefs*25) in the MCCC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC2 are known to be pathogenic (PMID: 11181649, 22642865). This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for MCCC2-related disease (PMID: 11170888, 16010683, 22642865). This variant is also known as D172fs. ClinVar contains an entry for this variant (Variation ID: 1919). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000598746 SCV000709818 pathogenic not provided 2018-01-23 criteria provided, single submitter clinical testing The c.517dupT variant in the MCCC2 gene has been reported previously in association with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Gallardo et al., 2001; Grunert et al., 2012). The c.517dupT variant is not observed in large population cohorts (Lek et al., 2016). The duplication causes a frameshift starting with codon serine 173, changes this amino acid to a Phenylalanine residue and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Ser173PhefsX25. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Baylor Genetics RCV000001996 SCV004194331 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-12-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000001996 SCV005666598 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2024-01-04 criteria provided, single submitter clinical testing
OMIM RCV000001996 SCV000022154 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2001-02-01 no assertion criteria provided literature only
Natera, Inc. RCV000001996 SCV002084290 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2020-07-13 no assertion criteria provided clinical testing

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