ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.517dup (p.Ser173fs) (rs587776533)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Invitae RCV000001996 SCV000644151 pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2017-11-14 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 6 of the MCCC2 mRNA (c.517dupT), causing a frameshift at codon 173. This creates a premature translational stop signal (p.Ser173Phefs*25) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC2 are known to be pathogenic. This particular variant has been observed as homozygous or in combination with other MCCC2 variants in symptomatic and asymptomatic individuals affected with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 11170888, 16010683, 22642865). This variant is also known as D172fs in the literature. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001996 SCV000022154 pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2001-02-01 no assertion criteria provided literature only

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