Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001379411 | SCV001577207 | pathogenic | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1067995). Disruption of this splice site has been observed in individuals with clinical features of megalencephalic leukoencephalopathy with subcortical cysts (PMID: 11935341, 32056211, 33084218; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 5 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003473919 | SCV004194995 | likely pathogenic | Megalencephalic leukoencephalopathy with subcortical cysts 1 | 2023-04-17 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001831368 | SCV002076187 | likely pathogenic | Megalencephalic leukoencephalopathy with subcortical cysts | 2020-01-03 | no assertion criteria provided | clinical testing |