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| 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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| Incidentalome v0.267 | CLU | Bryony Thompson Marked gene: CLU as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.267 | CLU | Bryony Thompson Gene: clu has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.267 | CLU | Bryony Thompson Phenotypes for gene: CLU were changed from to Alzheimer's Disease (MIM#104300) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.266 | CLU | Bryony Thompson Classified gene: CLU as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.266 | CLU | Bryony Thompson Gene: clu has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.230 | VCP | Sangavi Sivagnanasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21145000, 33004675; Phenotypes: Frontotemporal dementia and/or Amyotrophic lateral sclerosis 6 (MONDO:0013501, MIM 613954), Inclusion body myopathy with early-onset Paget Disease and FTD [IBMPFD] (MONDO:0000507MIM 167320); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.223 | CLU | Sangavi Sivagnanasundram reviewed gene: CLU: Rating: RED; Mode of pathogenicity: Other; Publications: 19734903, 20301340; Phenotypes: Alzheimer's Disease (MIM#104300); Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.169 | CACNA1C |
Zornitza Stark changed review comment from: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group DISPUTED for Brugada. Sources: Expert list |
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| Incidentalome v0.169 | CACNA1C |
Zornitza Stark changed review comment from: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Arrhythmia: definitive evidence for causality in Timothy syndrome but only moderate or limited evidence for isolated LQTS as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group Sources: Expert list |
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| Incidentalome v0.169 | CACNA1C |
Zornitza Stark changed review comment from: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Sources: Expert list; to: Association with HCM: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families. Sources: Expert list |
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| Incidentalome v0.163 | TPM1 |
Zornitza Stark changed review comment from: Several families reported, including ones with extensive segregation evidence; functional data, including animal model. MODERATE by ClinGen.; to: Several families reported, including ones with extensive segregation evidence; functional data, including animal model. MODERATE by ClinGen for DCM. DEFINITIVE for HCM. |
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| Incidentalome v0.126 | DSG2 |
Zornitza Stark edited their review of gene: DSG2: Added comment: Assessed as LIMITED by ClinGen for mono-allelic variants and DCM: Human genetic evidence supporting this gene-disease relationship includes one published definitive DCM case with truncating variant in DSG2 published by Garcia-Pavia et al (2011, PMID: 21859740). Of note, this person had limited ECG/arrhythmia phenotyping. Multiple other published variants have population frequencies which exclude them from scoring, as they are observed at a frequency higher than would be expected to have a pathogenic effect. In addition, this gene-disease association is supported by experimental evidence from postnatal DCM hearts showing reduced DSG2 signal in myocardium and other intercalated disc proteins were normal(Kessler et al, 2017, PMID: 28764973). In summary, there is limited evidence to support this gene-disease relationship. Bi-allelic variants and DCM: three families reported, two with missense variants. DEFINITIVE for ARVC.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193, Cardiomyopathy, dilated, 1BB, MIM# 612877; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Incidentalome v0.87 | ANXA11 | Zornitza Stark Phenotypes for gene: ANXA11 were changed from Amytrophic lateral sclerosis 23 MIM#617839 to Inclusion body myopathy and brain white matter abnormalities, MIM# 619733; Amyotrophic lateral sclerosis 23, MIM# 617839 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.85 | ANXA11 | Zornitza Stark reviewed gene: ANXA11: Rating: GREEN; Mode of pathogenicity: None; Publications: 34048612, 28469040; Phenotypes: Inclusion body myopathy and brain white matter abnormalities, MIM# 619733, Amyotrophic lateral sclerosis 23, MIM# 617839; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.69 | HTT | Bryony Thompson Added comment: Comment on list classification: Included on the panel as an STR under HD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Incidentalome v0.32 | BAP1 |
Zornitza Stark gene: BAP1 was added gene: BAP1 was added to Incidentalome. Sources: Expert list Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BAP1 were set to 21941004; 23684012; 21874000; 21874003 Phenotypes for gene: BAP1 were set to Tumor predisposition syndrome, MIM# 614327 Review for gene: BAP1 was set to GREEN Added comment: Generally adult onset, high-risk for the development of a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, and other cancer types, such as lung adenocarcinoma, meningioma, and renal cell carcinoma Sources: Expert list |
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| Incidentalome v0.0 | CLU |
Zornitza Stark gene: CLU was added gene: CLU was added to Incidentalome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CLU was set to Unknown |
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