ClinVar Miner

Submissions for variant NM_015166.4(MLC1):c.299_423+108del

dbSNP: rs1602049346
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817867 SCV000958450 pathogenic not provided 2023-12-28 criteria provided, single submitter clinical testing This variant results in the deletion of exon 5 and part of exon 4 (c.299_423+108del) of the MLC1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MLC1 are known to be pathogenic (PMID: 11254442, 16470554, 24824219). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of MLC1-related conditions (PMID: 16652334; Invitae). ClinVar contains an entry for this variant (Variation ID: 660628). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298788 SCV002598894 likely pathogenic Megalencephalic leukoencephalopathy with subcortical cysts 2022-09-14 criteria provided, single submitter clinical testing Variant summary: The variant identified by MLPA or other technology involves the partial deletion of exon 4 and full deletion of exon 5 in the MLC1 gene. A presumed nomenclature of c.299_423+108del557 has been designated for the purposes of this classification. This variant is expected to result in a large deletion in the MLC1 gene, a known mechanism of disease. The variant was absent in 21694 control chromosomes (gnomAD, Structural Variants dataset). A variant described as c.298_423+108del has been reported in the literature in a homozygous individual affected with Megalencephalic Leukoencephalopathy With Subcortical Cysts 1 (Boor_2006). These data indicate that the variant is likely to be associated with disease. A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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