ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.838G>T (p.Asp280Tyr) (rs119103226)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000002004 SCV000955887 likely pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2020-08-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 280 of the MCCC2 protein (p.Asp280Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs119103226, ExAC 0.06%). This variant has been observed to be homozygous or in combination with another MCCC2 variant in individuals affected with 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 28018443, 22150417, 22030835, 17968484). ClinVar contains an entry for this variant (Variation ID: 1927). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV000002004 SCV001622419 likely pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2021-05-13 criteria provided, single submitter clinical testing
OMIM RCV000002004 SCV000022162 pathogenic 3-methylcrotonyl CoA carboxylase 2 deficiency 2007-01-01 no assertion criteria provided literature only

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