Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001155001 | SCV001316399 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2018-01-12 | 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. |
| Revvity Omics, |
RCV001155001 | SCV003810817 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2021-02-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479284 | SCV004223246 | uncertain significance | not specified | 2023-11-29 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.914A>G (p.Glu305Gly) results in a non-conservative amino acid change located in the N-terminal domain (IPR011762) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251456 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in MCCC2 causing Methylcrotonyl-CoA Carboxylase Deficiency (6.4e-05 vs 0.0042), allowing no conclusion about variant significance. c.914A>G has been reported in the literature in at least one individual affected with Methylcrotonyl-CoA Carboxylase Deficiency (e.g., Cheng_2023). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 36822454). Three submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV004639483 | SCV005132491 | uncertain significance | Inborn genetic diseases | 2024-03-18 | criteria provided, single submitter | clinical testing | The c.914A>G (p.E305G) alteration is located in exon 10 (coding exon 10) of the MCCC2 gene. This alteration results from a A to G substitution at nucleotide position 914, causing the glutamic acid (E) at amino acid position 305 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001279170 | SCV001466252 | uncertain significance | Methylcrotonyl-CoA carboxylase deficiency | 2020-09-23 | no assertion criteria provided | clinical testing |