ClinVar Miner

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

gnomAD frequency: 0.00012  dbSNP: rs149957640
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Total submissions: 6
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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 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 521 of the MCCC1 protein (p.Ala521Thr). This variant is present in population databases (rs149957640, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 649123). 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. 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 Laboratory Services, 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].
Fulgent Genetics, Fulgent Genetics RCV000803982 SCV002798301 uncertain significance 3-methylcrotonyl-CoA carboxylase 1 deficiency 2022-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002534769 SCV003569442 uncertain significance Inborn genetic diseases 2022-04-07 criteria provided, single submitter clinical testing The c.1561G>A (p.A521T) alteration is located in exon 13 (coding exon 13) of the MCCC1 gene. This alteration results from a G to A substitution at nucleotide position 1561, causing the alanine (A) at amino acid position 521 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273451 SCV001456489 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-04-23 no assertion criteria provided clinical testing

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