Submissions for variant NM_015166.4(MLC1):c.594_597del (p.Ser197_Tyr198insTer)

dbSNP: rs267607236

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383177	SCV001582246	pathogenic	not provided	2023-11-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr198*) in the MLC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLC1 are known to be pathogenic (PMID: 11254442, 16470554, 24824219). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with megalencephalic leukoencephalopathy (PMID: 11254442, 11935341, 21555057). ClinVar contains an entry for this variant (Variation ID: 4720). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000004985	SCV002790027	pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1	2022-01-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000004985	SCV004194966	pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1	2023-11-09	criteria provided, single submitter	clinical testing
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000004985	SCV005187403	pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1	2021-02-09	criteria provided, single submitter	clinical testing	This variant (c.593_596del, p.Tyr198*) predicts a deletion resulting in a stop codon at tyrosine 198. It has been observed at very low frequency in population databases (gnomAD) and has been described in the literature (PMID 11254442). It was found in trans with a likely pathogenic variant (c.833A>G, p.Tyr278Cys) in an affected individual.
OMIM	RCV000004985	SCV000025161	pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1	2002-03-01	no assertion criteria provided	literature only
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,	RCV000004985	SCV002073668	likely pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts 1		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826417	SCV002076182	pathogenic	Megalencephalic leukoencephalopathy with subcortical cysts	2020-06-29	no assertion criteria provided	clinical testing