ClinVar Miner

Submissions for variant NM_015166.4(MLC1):c.178-10T>A

gnomAD frequency: 0.00001  dbSNP: rs80358243
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626926 SCV000747629 likely pathogenic Cerebellar ataxia; Macrocephaly; CNS demyelination 2017-01-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000020712 SCV001193820 likely pathogenic Megalencephalic leukoencephalopathy with subcortical cysts 1 2019-12-19 criteria provided, single submitter clinical testing NM_015166.3(MLC1):c.178-10T>A(aka IVS2-10T>A) is classified as likely pathogenic in the context of megalencephalic leukoencephalopathy with subcortical cysts. Sources cited for classification include the following: PMID 16652334 and 23851226. Classification of NM_015166.3(MLC1):c.178-10T>A(aka IVS2-10T>A) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses and is very rare or not present in genetic databases of healthy individuals. Please note: this variant was assessed in the context of healthy population screening.
Labcorp Genetics (formerly Invitae), Labcorp RCV002513148 SCV003444494 pathogenic not provided 2023-12-05 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the MLC1 gene. It does not directly change the encoded amino acid sequence of the MLC1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs80358243, gnomAD 0.0009%). This variant has been observed in individual(s) with megalencephalic leukoencephalopathy with subcortical cysts (PMID: 16652334, 23851226, 33084218). ClinVar contains an entry for this variant (Variation ID: 21522). Studies have shown that this variant results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 16652334, 23851226). This variant disrupts a region of the MLC1 protein in which other variant(s) (p.Gly73Glu) have been determined to be pathogenic (PMID: 21160490, 27322623; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000020712 SCV000041276 not provided Megalencephalic leukoencephalopathy with subcortical cysts 1 no assertion provided literature only

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