Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001775308 | SCV002012072 | likely pathogenic | Cerebellar atrophy, visual impairment, and psychomotor retardation; | 2021-10-02 | criteria provided, single submitter | clinical testing | Start-lost: reinitiation of translation may occur at a downstream alternate start codon but still result in a loss or disruption of normal protein function as there have been pathogenic variants reported upstream of the alterante start codon. (PVS1_M). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.00000399, PM2). Patient's phenotype is considered compatible with Cerebellar atrophy, visual impairment, and psychomotor retardation (3billion dataset, PP4). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV001885126 | SCV002108776 | pathogenic | not provided | 2021-10-03 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the EMC1 protein in which other variant(s) (p.Thr82Met) have been determined to be pathogenic (PMID: 26942288, 31904590). 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. This variant has not been reported in the literature in individuals affected with EMC1-related conditions. This sequence change affects the initiator methionine of the EMC1 mRNA. The next in-frame methionine is located at codon 90. This variant is present in population databases (rs762503667, ExAC 0.01%). |