ClinVar Miner

Submissions for variant NM_015166.4(MLC1):c.250C>T (p.Arg84Cys)

dbSNP: rs281875311
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000059743 SCV001574192 likely pathogenic not provided 2023-11-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 84 of the MLC1 protein (p.Arg84Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with megalencephalic leukoencephalopathy with subcortical cysts (PMID: 16652334, 31302377). ClinVar contains an entry for this variant (Variation ID: 68791). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MLC1 protein function. This variant disrupts the p.Arg84 amino acid residue in MLC1. Other variant(s) that disrupt this residue have been observed in individuals with MLC1-related conditions (PMID: 15832614, 25497041), which suggests that this may be a clinically significant amino acid residue. 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.
Baylor Genetics RCV003474653 SCV004194976 likely pathogenic Megalencephalic leukoencephalopathy with subcortical cysts 1 2023-11-09 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059743 SCV000091313 not provided not provided no assertion provided not provided
Natera, Inc. RCV001831812 SCV002076188 likely pathogenic Megalencephalic leukoencephalopathy with subcortical cysts 2020-07-20 no assertion criteria provided clinical testing

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.