Submissions for variant NM_015166.4(MLC1):c.268T>G (p.Cys90Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005088595	SCV005726527	uncertain significance	not specified	2024-11-19	criteria provided, single submitter	clinical testing	Variant summary: MLC1 c.268T>G (p.Cys90Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.268T>G has been reported in the literature in a homozygous individual affected with Megalencephalic Leukoencephalopathy With Subcortical Cysts 1 (Kariminejad_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25497041). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.