ClinVar Miner

Submissions for variant NM_001195518.2(MICU1):c.1A>G (p.Met1Val)

gnomAD frequency: 0.00001  dbSNP: rs747832014
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002043874 SCV002310649 uncertain significance not provided 2023-03-27 criteria provided, single submitter clinical testing 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1520093). Disruption of the initiator codon has been observed in individual(s) with MICU1-related conditions (PMID: 27159402). This variant is present in population databases (rs747832014, gnomAD 0.0009%). This sequence change affects the initiator methionine of the MICU1 mRNA. The next in-frame methionine is located at codon 34.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002086728 SCV002495842 uncertain significance Proximal myopathy with extrapyramidal signs 2021-03-30 criteria provided, single submitter clinical testing MICU1 NM_006077.3 exon 2 p.Met1? (c.1A>G): This variant has been reported in the literature as a compound heterozygote in 1 individual with congenital muscular dystrophy (O'Grady 2016 PMID:27159402). This variant is present in 0.001% (1/64572) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/10-72566793-T-C?dataset=gnomad_r3). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant creates a substitution at the first amino acid (Methionine) of this protein resulting in the loss of the start codon. However, a different methionine is present approximately 33 amino acids downstream (c.100) and may represent an alternate start codon for this protein. Further studies are needed to understand its impact. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV002043874 SCV002546702 pathogenic not provided 2022-06-09 criteria provided, single submitter clinical testing Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27159402)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.