ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.1561G>A (p.Ala521Thr) (rs149957640)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803982 SCV000943871 uncertain significance 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2018-10-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 521 of the MCCC1 protein (p.Ala521Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs149957640, ExAC 0.03%). This variant has not been reported in the literature in individuals with MCCC1-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000803982 SCV001309575 uncertain significance 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics RCV000803982 SCV001523029 uncertain significance 3 Methylcrotonyl-CoA carboxylase 1 deficiency 2020-09-17 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Natera, Inc. RCV001273451 SCV001456489 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-04-23 no assertion criteria provided clinical testing

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