Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV000790144 | SCV002012346 | pathogenic | Dejerine-Sottas disease | 2021-10-02 | criteria provided, single submitter | clinical testing | The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Gly100Gln) has been reported as pathogenic/likely pathogenic with strong evidence (PMID:9585367, PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.956, 3Cnet: 0.994, PP3). Patient's phenotype is considered compatible with Hypertrophic Neuropathy of Dejerine-Sottas (3billion dataset, PP4). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
Inherited Neuropathy Consortium | RCV000790144 | SCV000929535 | uncertain significance | Dejerine-Sottas disease | no assertion criteria provided | literature only |