Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668812 | SCV000793476 | likely pathogenic | Megalencephalic leukoencephalopathy with subcortical cysts 1 | 2017-08-16 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000668812 | SCV004195004 | likely pathogenic | Megalencephalic leukoencephalopathy with subcortical cysts 1 | 2023-01-30 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768531 | SCV005381204 | likely pathogenic | Megalencephalic leukoencephalopathy with subcortical cysts | 2024-08-07 | criteria provided, single submitter | clinical testing | Variant summary: MLC1 c.634G>C (p.Gly212Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250780 control chromosomes. c.634G>C has been reported in the literature in at least one biallelic individual affected with Megalencephalic Leukoencephalopathy With Subcortical Cysts 1 (e.g. Duarri_2008). One publication reports experimental evidence evaluating an impact on protein function showing reduced expression of the MLC1 protein at the plasma membrane in vitro (e.g. Teijido_2004), however, does not allow convincing conclusions about the variant effect. A different variant resulting in the same amino acid change (c.634G>A, p.Gly212Arg) has been previously classified as Likely pathogenic by our lab. ClinVar contains an entry for this variant (Variation ID: 553381). Based on the evidence outlined above, the variant was classified as likely pathogenic. |