Submissions for variant NM_015166.4(MLC1):c.833A>G (p.Tyr278Cys)

dbSNP: rs1569244190

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000768440	SCV001132555	uncertain significance	Megalencephalic leukoencephalopathy with subcortical cysts 1	2018-11-15	criteria provided, single submitter	research	The homozygous p.Tyr278Cys variant in MLC1 was identified by our study in an individual with Megalencephalic Leukoencephalopathy with Subcortical Cysts. This variant was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro441Leu variant is uncertain.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000768440	SCV004175737	uncertain significance	Megalencephalic leukoencephalopathy with subcortical cysts 1	2023-12-12	criteria provided, single submitter	clinical testing
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000768440	SCV005187392	likely pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1	2021-02-10	criteria provided, single submitter	clinical testing	This missense variant (c.833A>G, p.Tyr278Cys) has not been observed in population databases, although it has been reported in the literature (PMID 31178897). There is no consensus as to the classification of this change based on variant prediction programs, and no functional studies have been published. It has been found in trans with a likely pathogenic variant (c.593_596 del, p.Tyr198*) in an affected individual.
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768440	SCV000899200	likely pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1		no assertion criteria provided	case-control