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| Schwannoma v0.13 | SMARCB1 | Zornitza Stark Marked gene: SMARCB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.13 | SMARCB1 | Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.12 | SMARCB1 |
Chirag Patel changed review comment from: ClinGen definitive Schwannomas reported in condition Sources: Expert list, Expert Review; to: ClinGen definitive. Schwannomas reported in condition. Sources: Expert list, Expert Review |
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| Schwannoma v0.12 | SMARCA4 |
Chirag Patel gene: SMARCA4 was added gene: SMARCA4 was added to Schwannoma. Sources: Expert Review,Literature Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCA4 were set to PMID: 36786840 Phenotypes for gene: SMARCA4 were set to Schwannoma, MONDO:0002546; Rhabdoid tumor predisposition syndrome 2, MONDO:0013224; Rhabdoid tumor predisposition syndrome 2, MIM#613325 Review for gene: SMARCA4 was set to RED Added comment: ClinGen definitive for RTPS2 1 family with 3 affected individuals with adult-onset schwannomas (2/3), glioblastoma (1/3), and malignant peripheral nerve sheath tumour (1/3). Whole-genome sequencing in proband identified a variant in SMARCA4 gene ([c.1752_1755del, p.(Lys585Argfs*27). In the schwannomas, immunohistochemical (IHC) staining showed loss of BRG1 (SMARCA4) expression in 80–90% of cells and loss of INI1 (SMARCB1) in the complementary 10–20% of cells in all 5 schwannomas but complete retention of BRG1 and INI1 in the glioblastoma. Whole exome sequencing (WES) of DNA from proband's blood, mother’s normal skin, all 5 schwannomas and the glioblastoma, confirmed the presence of the truncating SMARCA4 LPV in all samples. LOH was observed at the SMARCA4 locus, extending to 12–23 Mb of Chromosome 19p (Chr19p) in all schwannomas, but not in the glioblastoma. No LOH of Chr22q was detected in the schwannomas. The germline SMARCA4 variant was also detected in proband's maternal grandfather’s MPNST in a heterozygous state. Sources: Expert Review, Literature |
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| Schwannoma v0.9 | LZTR1 |
Chirag Patel gene: LZTR1 was added gene: LZTR1 was added to Schwannoma. Sources: Expert list,Expert Review Mode of inheritance for gene: LZTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LZTR1 were set to PMID: 24362817, 29517885 Phenotypes for gene: LZTR1 were set to Schwannoma, MONDO:0002546; Schwannomatosis 2, MONDO:0014299; Schwannomatosis, susceptibility to, 2, MIM#615670 Review for gene: LZTR1 was set to GREEN gene: LZTR1 was marked as current diagnostic Added comment: 15 different germline heterozygous mutations in the LZTR1 gene identified in 16/20 probands with schwannomatosis. There were 6 truncating mutations, 1 in-frame splice site mutation, 1 deletion affecting a splice site, and 7 missense mutations at highly conserved residues. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. All schwannomas studied also carried the heterozygous LZTR1 mutation, and all showed loss of heterozygosity (LOH) at chromosome 22q11, including the LZTR1, NF2, and SMARCB1 genes. In addition, all tumours carried a heterozygous somatic mutation in the NF2 gene. These findings were consistent with biallelic loss of function of both LZTR1 and NF2 in all tumours. Functional studies of the variants were not performed. Pathogenesis of tumour characterised as resulting from 3 mutational events: a germline LZTR1 mutation (E1), a deletion of 22q that includes the LZTR1 and NF2 genes (E2), and a somatic NF2 mutation (E3). Loss of LZTR1 function can predispose to the development of autosomal dominant multiple schwannomas, thus implicating LZTR1 as a tumor suppressor gene. Sources: Expert list, Expert Review |
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| Schwannoma v0.4 | SMARCB1 | Chirag Patel Classified gene: SMARCB1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.4 | SMARCB1 | Chirag Patel Gene: smarcb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Schwannoma v0.3 | SMARCB1 |
Chirag Patel gene: SMARCB1 was added gene: SMARCB1 was added to Schwannoma. Sources: Expert list,Expert Review Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SMARCB1 were set to Schwannoma, MONDO:0002546; Schwannomatosis 1, MONDO:0024517; Rhabdoid tumor predisposition syndrome 1, MONDO:0012252; Rhabdoid tumor predisposition syndrome 1, MIM#609322; Schwannomatosis, susceptibility to, 1, MIM#162091 Review for gene: SMARCB1 was set to GREEN gene: SMARCB1 was marked as current diagnostic Added comment: ClinGen definitive Schwannomas reported in condition Sources: Expert list, Expert Review |
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