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| Mosaic skin disorders - deep sequencing v3.16 | TSC1 | Ida Ertmanska changed review comment from: Comment on list classification: There are numerous individuals reported in literature diagnosed with Tuberous sclerosis complex, harbouring heterozygous mosaic TSC1 variants. Deep sequencing of multiple patient samples is advised, as the variants often occur at very low frequencies (3-5%). Variants may be detected in skin biopsy samples but not in blood or saliva. Based on the available evidence, TSC1 should be promoted to Green for Mosaic skin disorders - deep sequencing.; to: Comment on list classification: There are numerous individuals reported in literature diagnosed with Tuberous sclerosis complex, harbouring heterozygous mosaic TSC1 variants. Deep sequencing of multiple patient samples is advised, as the variants often occur at very low frequencies (3-5%). Variants are sometimes detected in skin biopsy samples only - not in blood or saliva. Based on the available evidence, TSC1 should be promoted to Green for Mosaic skin disorders - deep sequencing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.16 | TSC1 |
Ida Ertmanska changed review comment from: Tuberous sclerosis complex present with hamartomatous tumors affecting multiple organs, including the skin: facial angiofibroma, ungual fibroma, and shagreen patch (PMID: 37141891). PMID: 37356622 Blasco-Perez et al., 2023 Cohort of Tuberous sclerosis complex (TSC) patients. Seq method: deep coverage NGS seq of TSC1 and TSC2 - average coverage >400x. 8/29 variants were detected in mosaicism, 4 at extremely low levels ( <16%). Patients with TSC1 variants: 10 non-mosaic heterozygous cases; Patient 6: mosaic variant TSC1:c.994del, p.Ser332Profs∗6; variant detected in saliva (36%) and affected skin (42%); blood sequencing not performed Patient 12: mosaic variant TSC1:c.2101_2107del, p.Gln701Serfs∗21 - 4% in peripheral blood PMID: 37141891 Klonowska et al., 2023 Cohort of 95 individuals with TSC and confirmed mosaicism. Method: Deep massively parallel sequencing (MPS) (median read depth ≥ 500×). 9/95 individuals had variants in TSC1, and 86/95 patients had variants detected in TCS2. The cohort included patients previously reported in PMID: 26540169 Tyburczy et al., 2015, as well as PMID: 31160751 Giannikou et al., 2019; PMID: 31114024 Treichel et al., 2019; PMID: 32461669 Ogorek et al., 2020. PMID: 26540169 Tyburczy et al., 2015 Cohort of 53 patients with TSC and no mutation identified in previous testing. Median read depth was ≥ 5,000x for long-range PCR, and ≥ 500x in hybrid capture method. All 53 TSC patients had skin involvement. Reported 4 patients with non-mosaic heterozygous TSC1 variants (allele freq = 50%), as well as 4 mosaic cases (allele freq <50%): P53: 22yo male; TSC1 c.1776delG - 30% mutant allele in saliva and blood P2: 20yo male; c.2689C>T; p.Q897* in TSC1 - 15% mutant allele in blood P6: 4yo male; TSC1 c.2111_2112delAT - 4.7% in blood and normal skin P5f: 57yo female; TSC1 c.2374C>T; p.Q792* - 3.3% in blood This gene is associated with AD Tuberous sclerosis-1, MIM:191100 in OMIM (accessed 3rd Dec 2025).; to: Tuberous sclerosis complex present with hamartomatous tumors affecting multiple organs, including the skin: facial angiofibroma, ungual fibroma, and shagreen patch (PMID: 37141891). PMID: 37356622 Blasco-Perez et al., 2023 Cohort of Tuberous sclerosis complex (TSC) patients. Seq method: deep coverage NGS seq of TSC1 and TSC2 - average coverage >400x. 8/29 variants were detected in mosaicism, 4 at extremely low levels ( <16%). Variants are sometimes detected in skin biopsy samples only - not in blood or saliva. Patients with TSC1 variants: 10 non-mosaic heterozygous cases; Patient 6: mosaic variant TSC1:c.994del, p.Ser332Profs∗6; variant detected in saliva (36%) and affected skin (42%); blood sequencing not performed Patient 12: mosaic variant TSC1:c.2101_2107del, p.Gln701Serfs∗21 - 4% in peripheral blood PMID: 37141891 Klonowska et al., 2023 Cohort of 95 individuals with TSC and confirmed mosaicism. Method: Deep massively parallel sequencing (MPS) (median read depth ≥ 500×). 9/95 individuals had variants in TSC1, and 86/95 patients had variants detected in TCS2. The cohort included patients previously reported in PMID: 26540169 Tyburczy et al., 2015, as well as PMID: 31160751 Giannikou et al., 2019; PMID: 31114024 Treichel et al., 2019; PMID: 32461669 Ogorek et al., 2020. PMID: 26540169 Tyburczy et al., 2015 Cohort of 53 patients with TSC and no mutation identified in previous testing. Median read depth was ≥ 5,000x for long-range PCR, and ≥ 500x in hybrid capture method. All 53 TSC patients had skin involvement. Reported 4 patients with non-mosaic heterozygous TSC1 variants (allele freq = 50%), as well as 4 mosaic cases (allele freq <50%): P53: 22yo male; TSC1 c.1776delG - 30% mutant allele in saliva and blood P2: 20yo male; c.2689C>T; p.Q897* in TSC1 - 15% mutant allele in blood P6: 4yo male; TSC1 c.2111_2112delAT - 4.7% in blood and normal skin P5f: 57yo female; TSC1 c.2374C>T; p.Q792* - 3.3% in blood This gene is associated with AD Tuberous sclerosis-1, MIM:191100 in OMIM (accessed 3rd Dec 2025). |
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| Mosaic skin disorders - deep sequencing v3.16 | TSC1 | Ida Ertmanska Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.16 | TSC1 | Ida Ertmanska changed review comment from: Comment on list classification: There are numerous individuals reported in literature diagnosed with Tuberous sclerosis complex, harbouring mosaic TSC1 variants. Deep sequencing of multiple patient samples is advised, as the variants often occur at very low frequencies (3-5%). Variants may be detected in skin biopsy samples but not in blood or saliva. Based on the available evidence, TSC1 should be promoted to Green for Mosaic skin disorders - deep sequencing.; to: Comment on list classification: There are numerous individuals reported in literature diagnosed with Tuberous sclerosis complex, harbouring heterozygous mosaic TSC1 variants. Deep sequencing of multiple patient samples is advised, as the variants often occur at very low frequencies (3-5%). Variants may be detected in skin biopsy samples but not in blood or saliva. Based on the available evidence, TSC1 should be promoted to Green for Mosaic skin disorders - deep sequencing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.16 | TSC1 | Ida Ertmanska Phenotypes for gene: TSC1 were changed from Cutaneous pigmentary abnormalities, and/or other aspects of germline TSC disease to Tuberous sclerosis-1, OMIM:191100; tuberous sclerosis 1, MONDO:0008612 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.15 | TSC1 | Ida Ertmanska Publications for gene: TSC1 were set to PMID: 37356622 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.14 | TSC1 | Ida Ertmanska Mode of inheritance for gene: TSC1 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.13 | TSC1 | Ida Ertmanska Added comment: Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.13 | TSC1 | Ida Ertmanska Mode of inheritance for gene: TSC1 was changed from Other to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.12 | TSC1 | Ida Ertmanska Classified gene: TSC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.12 | TSC1 | Ida Ertmanska Gene: tsc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.11 | TSC1 |
Ida Ertmanska Tag Q4_25_promote_green tag was added to gene: TSC1. Tag Q4_25_NHS_review tag was added to gene: TSC1. |
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| Mosaic skin disorders - deep sequencing v3.11 | TSC1 | Ida Ertmanska commented on gene: TSC1: Comment on list classification: There are numerous individuals reported in literature diagnosed with Tuberous sclerosis complex, harbouring mosaic TSC1 variants. Deep sequencing of multiple patient samples is advised, as the variants often occur at very low frequencies (3-5%). Variants may be detected in skin biopsy samples but not in blood or saliva. Based on the available evidence, TSC1 should be promoted to Green for Mosaic skin disorders - deep sequencing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.11 | TSC1 |
Ida Ertmanska changed review comment from: Tuberous sclerosis complex present with hamartomatous tumors affecting multiple organs, including the skin: facial angiofibroma, ungual fibroma, shagreen patch. PMID: 37356622 Blasco-Perez et al., 2023 Cohort of Tuberous sclerosis complex (TSC) patients. Seq method: deep coverage NGS seq of TSC1 and TSC2 - average coverage >400x. 8/29 variants were detected in mosaicism, 4 at extremely low levels ( <16%). Patients with TSC1 variants: 10 non-mosaic heterozygous cases; Patient 6: mosaic variant TSC1:c.994del, p.Ser332Profs∗6; variant detected in saliva (36%) and affected skin (42%); blood sequencing not performed Patient 12: mosaic variant TSC1:c.2101_2107del, p.Gln701Serfs∗21 - 4% in peripheral blood PMID: 37141891 Klonowska et al., 2023 Cohort of 95 individuals with TSC and confirmed mosaicism. Method: Deep massively parallel sequencing (MPS) (median read depth ≥ 500×). 9/95 individuals had variants in TSC1, and 86/95 patients had variants detected in TCS2. The cohort included patients previously reported in PMID: 26540169 Tyburczy et al., 2015, as well as PMID: 31160751 Giannikou et al., 2019; PMID: 31114024 Treichel et al., 2019; PMID: 32461669 Ogorek et al., 2020. PMID: 26540169 Tyburczy et al., 2015 Cohort of patients with TSC and no mutation identified in previous testing. Median read depth was ≥ 5,000x for long-range PCR, and ≥ 500x in hybrid capture method. Reported 4 patients with non-mosaic heterozygous TSC1 variants (allele freq = 50%), as well as 4 mosaic cases (allele freq <50%): P53: 22yo male; TSC1 c.1776delG - 30% mutant allele in saliva and blood P2: 20yo male; c.2689C>T; p.Q897* in TSC1 - 15% mutant allele in blood P6: 4yo male; TSC1 c.2111_2112delAT - 4.7% in blood and normal skin P5f: 57yo female; TSC1 c.2374C>T; p.Q792* - 3.3% in blood This gene is associated with AD Tuberous sclerosis-1, MIM:191100 in OMIM (accessed 3rd Dec 2025).; to: Tuberous sclerosis complex present with hamartomatous tumors affecting multiple organs, including the skin: facial angiofibroma, ungual fibroma, and shagreen patch (PMID: 37141891). PMID: 37356622 Blasco-Perez et al., 2023 Cohort of Tuberous sclerosis complex (TSC) patients. Seq method: deep coverage NGS seq of TSC1 and TSC2 - average coverage >400x. 8/29 variants were detected in mosaicism, 4 at extremely low levels ( <16%). Patients with TSC1 variants: 10 non-mosaic heterozygous cases; Patient 6: mosaic variant TSC1:c.994del, p.Ser332Profs∗6; variant detected in saliva (36%) and affected skin (42%); blood sequencing not performed Patient 12: mosaic variant TSC1:c.2101_2107del, p.Gln701Serfs∗21 - 4% in peripheral blood PMID: 37141891 Klonowska et al., 2023 Cohort of 95 individuals with TSC and confirmed mosaicism. Method: Deep massively parallel sequencing (MPS) (median read depth ≥ 500×). 9/95 individuals had variants in TSC1, and 86/95 patients had variants detected in TCS2. The cohort included patients previously reported in PMID: 26540169 Tyburczy et al., 2015, as well as PMID: 31160751 Giannikou et al., 2019; PMID: 31114024 Treichel et al., 2019; PMID: 32461669 Ogorek et al., 2020. PMID: 26540169 Tyburczy et al., 2015 Cohort of 53 patients with TSC and no mutation identified in previous testing. Median read depth was ≥ 5,000x for long-range PCR, and ≥ 500x in hybrid capture method. All 53 TSC patients had skin involvement. Reported 4 patients with non-mosaic heterozygous TSC1 variants (allele freq = 50%), as well as 4 mosaic cases (allele freq <50%): P53: 22yo male; TSC1 c.1776delG - 30% mutant allele in saliva and blood P2: 20yo male; c.2689C>T; p.Q897* in TSC1 - 15% mutant allele in blood P6: 4yo male; TSC1 c.2111_2112delAT - 4.7% in blood and normal skin P5f: 57yo female; TSC1 c.2374C>T; p.Q792* - 3.3% in blood This gene is associated with AD Tuberous sclerosis-1, MIM:191100 in OMIM (accessed 3rd Dec 2025). |
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| Mosaic skin disorders - deep sequencing v3.11 | TSC1 | Ida Ertmanska reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26540169, 31160751, 31114024, 32461669, 37141891, 37356622; Phenotypes: Tuberous sclerosis-1, OMIM:191100, tuberous sclerosis 1, MONDO:0008612; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.1 | TSC1 | Veronica Kinsler edited their review of gene: TSC1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v3.1 | TSC1 |
Veronica Kinsler gene: TSC1 was added gene: TSC1 was added to Mosaic skin disorders - deep sequencing. Sources: Expert Review Mode of inheritance for gene: TSC1 was set to Other Publications for gene: TSC1 were set to PMID: 37356622 Phenotypes for gene: TSC1 were set to Cutaneous pigmentary abnormalities, and/or other aspects of germline TSC disease Added comment: Mosaic, potential for germline transmission to offspring Sources: Expert Review |
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