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| Incidentalome v0.301 | SS18L1 | Zornitza Stark Marked gene: SS18L1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.301 | SS18L1 | Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.301 | SS18L1 | Zornitza Stark Classified gene: SS18L1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.301 | SS18L1 | Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.300 | SS18L1 |
Zornitza Stark gene: SS18L1 was added gene: SS18L1 was added to Incidentalome. Sources: Expert Review Mode of inheritance for gene: SS18L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SS18L1 were set to 25888396; 24360741; 23708140; 30976389 Phenotypes for gene: SS18L1 were set to amyotrophic lateral sclerosis (MONDO:0004976) Review for gene: SS18L1 was set to AMBER Added comment: ClinGen has curated as LIMITED: There are 5 variants (one nonsense, three missense, and one in-frame del) that have been reported in 5 probands in 3 publications (PMIDs: 23708140, 24360741, 31522742) that are included in this curation, one of which was not scored due to the patient harboring a variant in another ALS-causing gene and a high minor allele frequency in population databases. ALS-associated SS18L1 variants are suggested to dysregulate neuronal function by inhibiting dendrite outgrowth and microglial activation through a dominant-negative mechanism, however there is an absence of functional data from primary tissue of SS18L1 mutation carriers. This gene-disease relationship is also supported by experimental evidence (mouse models, expression, and protein interactions; PMIDs: 30976389, 14716005, 23708140). CREST knockout (Crest +/− ) and Q394X knock-in mice generated through CRISPR/Cas9 system displayed deficits in motor coordination and partially recapitulated ALS phenotypes (PMID: 30976389). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. Sources: Expert Review |
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