ClinVar Miner

Submissions for variant NM_015166.4(MLC1):c.710T>A (p.Val237Glu)

gnomAD frequency: 0.00002  dbSNP: rs765967624
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004494794 SCV004987498 uncertain significance Inborn genetic diseases 2021-12-03 criteria provided, single submitter clinical testing The c.710T>A (p.V237E) alteration is located in exon 8 (coding exon 7) of the MLC1 gene. This alteration results from a T to A substitution at nucleotide position 710, causing the valine (V) at amino acid position 237 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005407307 SCV006072583 uncertain significance not specified 2025-04-08 criteria provided, single submitter clinical testing Variant summary: MLC1 c.710T>A (p.Val237Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-05 in 246854 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in MLC1 causing Megalencephalic Leukoencephalopathy with Subcortical Cysts 1 (4.1e-05 vs 0.0011), allowing no conclusion about variant significance. c.710T>A has been reported in the literature in at least an individual affected with MLC1-related conditions (Passchier_2024). This report, however, does not provide unequivocal conclusions about association of the variant with Megalencephalic Leukoencephalopathy with Subcortical Cysts 1. 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: 38487253). ClinVar contains an entry for this variant (Variation ID: 3196935). Based on the evidence outlined above, the variant was classified as uncertain significance.

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