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Incidentalome v0.316 HTT_HD_CAG Bryony Thompson HD was changed to HTT_HD_CAG
Incidentalome v0.315 C9orf72_FTDALS_GGGGCC Bryony Thompson FTDALS was changed to C9orf72_FTDALS_GGGGCC
Incidentalome v0.307 DICER1 Zornitza Stark Mode of inheritance for gene: DICER1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.306 CDH1 Zornitza Stark Mode of inheritance for gene: CDH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.305 CACNA1S Zornitza Stark Phenotypes for gene: CACNA1S were changed from to Malignant hyperthermia susceptibility 5, MIM# 601887
Incidentalome v0.304 CACNA1S Zornitza Stark Mode of inheritance for gene: CACNA1S was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.302 APOE Zornitza Stark Mode of inheritance for gene: APOE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.299 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9, MIM# 609040 to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Dilated cardiomyopathy, MONDO:0005021, PKP2-related
Incidentalome v0.297 PKP2 Zornitza Stark Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.296 PKP2 Zornitza Stark edited their review of gene: PKP2: Added comment: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.

PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).

PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.; Changed publications: 30562116, 35059364, 38050058
Incidentalome v0.296 PKP2 Zornitza Stark edited their review of gene: PKP2: Changed phenotypes: Arrhythmogenic right ventricular dysplasia 9, MIM# 609040, Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.295 CCNF Zornitza Stark edited their review of gene: CCNF: Changed rating: AMBER
Incidentalome v0.295 MLH1 Bryony Thompson Mode of inheritance for gene: MLH1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.294 MLH1 Bryony Thompson Phenotypes for gene: MLH1 were changed from to mismatch repair cancer syndrome 1 MONDO:0010159
Incidentalome v0.293 MEN1 Bryony Thompson Phenotypes for gene: MEN1 were changed from to Multiple endocrine neoplasia 1, MIM# 131100
Incidentalome v0.292 MEN1 Bryony Thompson Mode of inheritance for gene: MEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.291 MAPT Bryony Thompson Phenotypes for gene: MAPT were changed from to Supranuclear palsy, progressive (MIM# 601104) AD; Supranuclear palsy, progressive atypical (MIM# 260540) AR
Incidentalome v0.289 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.288 LRRK2 Bryony Thompson Phenotypes for gene: LRRK2 were changed from to Parkinson Disease type 8 (MONDO:0005180, MIM#607060)
Incidentalome v0.287 LRRK2 Bryony Thompson Mode of pathogenicity for gene: LRRK2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Incidentalome v0.285 LRRK2 Bryony Thompson Mode of inheritance for gene: LRRK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.283 LDLR Bryony Thompson Phenotypes for gene: LDLR were changed from to Hypercholesterolemia, familial, 1, MIM# 143890
Incidentalome v0.282 LDLR Bryony Thompson Mode of inheritance for gene: LDLR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.280 ITM2B Bryony Thompson Mode of pathogenicity for gene: ITM2B was changed from None to Other
Incidentalome v0.279 GRN Bryony Thompson Phenotypes for gene: GRN were changed from to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Incidentalome v0.277 GRN Bryony Thompson Mode of inheritance for gene: GRN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.275 GBA Bryony Thompson Phenotypes for gene: GBA were changed from to Parkinson's disease, MONDO:0005180, GBA-related
Incidentalome v0.274 GBA Bryony Thompson Mode of inheritance for gene: GBA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.273 FUS Bryony Thompson Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030
Incidentalome v0.271 FUS Bryony Thompson Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.270 FTL Bryony Thompson Phenotypes for gene: FTL were changed from to Neurodegeneration with brain iron accumulation 3, MIM# 606159
Incidentalome v0.268 FTL Bryony Thompson Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.267 CLU Bryony Thompson Phenotypes for gene: CLU were changed from to Alzheimer's Disease (MIM#104300)
Incidentalome v0.265 CHMP2B Bryony Thompson Phenotypes for gene: CHMP2B were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795; MONDO:0010936)
Incidentalome v0.263 CHMP2B Bryony Thompson Mode of pathogenicity for gene: CHMP2B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Incidentalome v0.262 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.262 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.258 BRCA2 Bryony Thompson Phenotypes for gene: BRCA2 were changed from to Breast-ovarian cancer, familial, 2, MIM#612555
Incidentalome v0.257 BRCA2 Bryony Thompson Mode of inheritance for gene: BRCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.256 BRCA1 Bryony Thompson Phenotypes for gene: BRCA1 were changed from to Breast-ovarian cancer, familial, 1, MIM# 604370
Incidentalome v0.255 BRCA1 Bryony Thompson Mode of inheritance for gene: BRCA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.253 ATP7B Bryony Thompson Mode of inheritance for gene: ATP7B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.252 ATP7B Bryony Thompson Phenotypes for gene: ATP7B were changed from to Wilson Disease (MONDO:0010200; MIM #277900)
Incidentalome v0.251 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to Kufor-Rakeb syndrome, MIM# 606693
Incidentalome v0.250 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.249 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer's Disease (MIM#104300)
Incidentalome v0.247 APP Bryony Thompson Mode of pathogenicity for gene: APP was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Incidentalome v0.246 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.245 APOE Bryony Thompson Phenotypes for gene: APOE were changed from Alzheimer disease 2, MIM# 104310 to Alzheimer disease 2, MIM# 104310; Hyperlipoproteinemia, type III (MIM#617347); Sea-blue histiocyte disease (MIM#269600)
Incidentalome v0.243 APOE Bryony Thompson Phenotypes for gene: APOE were changed from to Alzheimer disease 2, MIM# 104310
Incidentalome v0.242 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.241 APOB Bryony Thompson Phenotypes for gene: APOB were changed from to Hypercholesterolemia, familial, 2, MIM# 144010
Incidentalome v0.240 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.238 ANG Bryony Thompson Marked gene: ANG as ready
Incidentalome v0.238 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Incidentalome v0.238 ANG Bryony Thompson Phenotypes for gene: ANG were changed from to Amyotrophic Lateral Sclerosis (MONDO: 0012753; MIM#611895)
Incidentalome v0.237 ANG Bryony Thompson Publications for gene: ANG were set to
Incidentalome v0.236 ANG Bryony Thompson Tag neurological tag was added to gene: ANG.
Incidentalome v0.236 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Incidentalome v0.235 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Incidentalome v0.232 POT1 Zornitza Stark Phenotypes for gene: POT1 were changed from Tumour predisposition with variety of solid and haematological malignancies reported. to Hereditary neoplastic syndrome, MONDO:0015356, POT1-related
Incidentalome v0.230 UBQLN2 Sangavi Sivagnanasundram edited their review of gene: UBQLN2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.230 UBQLN2 Sangavi Sivagnanasundram changed review comment from: Established gene identified in many individuals with ALS and/or dementia however there is conflicting evidence on the mode of pathogenicity.

PMID: 21857683 – 3 unrelated individuals with missense mutations (P497S, P509S, P525S) causative of UBQLN2- related ALS and ALS/Dementia.

PMID: 31319884 Reports on multiple articles conducting functional studies with evidence supporting that mutations in UBQLN2 impair the UPS pathway.

PMID: 26152284 – In vivo mouse model that showed that UBQLN2 mutants cause neurodegeneration and aggregate formation however the gene-disease association link wasn’t identified.

PMID: 25388785 – transgenic knockout rat model showed that mutant UBQLN2 cells lead to aggregation formation. Cresyl violet staining in the rats showed a reduction in neuron density which led to neurodegeneration. Neural impairment in the rats were confirmed by Golgi staining and was shown to have a distorted structure of cortex.; to: Established gene identified in many individuals with ALS and/or dementia however there is conflicting evidence on the mode of pathogenicity.

PMID: 21857683 – 3 unrelated individuals with missense mutations (P497S, P509S, P525S) causative of UBQLN2- related ALS and ALS/Dementia.

PMID: 31319884 Reports on multiple articles conducting functional studies with evidence supporting that mutations in UBQLN2 impair the UPS pathway.

PMID: 26152284 – In vivo mouse model that showed that UBQLN2 mutants cause neurodegeneration and aggregate formation however the gene-disease association link wasn’t identified.

PMID: 25388785 – transgenic knockout rat model showed that mutant UBQLN2 cells lead to aggregation formation. Cresyl violet staining in the rats showed a reduction in neuron density which led to neurodegeneration. Neural impairment in the rats were confirmed by Golgi staining and was shown to have a distorted structure of cortex.
Incidentalome v0.229 PSEN2 Sangavi Sivagnanasundram changed review comment from: Well established rare cause of Alzheimer Disease.

PMID: 10652366: In vitro functional assay shows that a mutation in the PSEN2 gene causes an effect to the endoproteolytic processing of the transmembrane protein thus a loss of function to the transmembrane protein.

PMID: 7638622: (Article refers to gene in previously terminology of STM2)
N141I founder mutation was identified in 20 individuals from 5 Volgan German families.
The point mutation is present in the conserved human and mouse homolog (S182).

PMID: 12925374: A spanish individual identified with a T430M mutation (a common variant reported in the Latino/Admixed American population but at a low frequency [PopMax AF 0.01%]).; to: Well established rare cause of Alzheimer Disease.

PMID: 10652366: In vitro functional assay shows that a mutation in the PSEN2 gene causes an effect to the endoproteolytic processing of the transmembrane protein thus a loss of function to the transmembrane protein.

PMID: 7638622: (Article refers to gene in previously terminology of STM2)
N141I founder mutation was identified in 20 individuals from 5 Volgan German families.
The point mutation is present in the conserved human and mouse homolog (S182).

PMID: 12925374: A spanish individual identified with a T430M mutation (a common variant reported in the Latino/Admixed American population but at a low frequency [PopMax AF 0.01%]).
Incidentalome v0.229 PCSK9 Zornitza Stark Phenotypes for gene: PCSK9 were changed from to Familial Hypercholesterolemia 3 (MONDO:0011369; MIM# 603776); Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1; MIM# 603776)
Incidentalome v0.227 PCSK9 Zornitza Stark Mode of inheritance for gene: PCSK9 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.226 PARK7 Sangavi Sivagnanasundram changed review comment from: Note that the gene was renamed from DJ1 to PARK7 (articles and OMIM reference our gene with previous name)

Variants in PARK7 (DJ1) gene are a rare cause of Parkinson Disease and is currently only reported in 3 individuals from 3 unrelated families.

PMID: 11462174; 11835383 – 2 individuals from 2 unrelated families with variants in DJ1 that were causative of Parkinson Disease.

PMID: 16240358 – 3 affected sibs from a consanguineous Italian family; to: Note that the gene was renamed from DJ1 to PARK7 (articles and OMIM reference our gene with previous name)

Variants in PARK7 (DJ1) gene are a rare cause of Parkinson Disease and is currently only reported in 3 individuals from 3 unrelated families.

PMID: 11462174; 11835383 – 2 individuals from 2 unrelated families with variants in DJ1 that were causative of Parkinson Disease.

PMID: 16240358 – 3 affected sibs from a consanguineous Italian family
Incidentalome v0.226 FA2H Zornitza Stark Phenotypes for gene: FA2H were changed from to Spastic Paraplegia (MIM#612319)
Incidentalome v0.224 FA2H Zornitza Stark Mode of inheritance for gene: FA2H was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.223 CALHM1 Sangavi Sivagnanasundram changed review comment from: PMID:19472444 – Study to identify whether mutation sin CALHM1 had any correlation to Alzheimers Disease. Study showed no association between CALHM1 and Alzheimers Disease; to: PMID:19472444 – Study to identify whether mutations in CALHM1 had any correlation to Alzheimers Disease. Study showed no association between CALHM1 and Alzheimers Disease (AD)

No evidence showing correlation between CALHM1 mutations and AD
Incidentalome v0.223 APP Sangavi Sivagnanasundram changed review comment from: PubMed: 17121991: transgenic mouse study identified that hypoxia increase BACE1 activity which resulted in a significant increase in the production of beta-amyloid in AD-related APP mutations. The study showed that hypoxia up-regulated Bace1 mRNA and increased deposition of beta proteins.

PMID: 1520398 – V717I variant identified in multiple members in a Canadian family of European decent with a dominant inheritance of Alzheimers disease
PMID: 15365148 – 1 family with 6 affected individuals over 3 generations with heterozygous mutations in APP gene – phenotypic features of Alzheimers. Individuals had MRI conducted showing multiple white matter infarcts along the long penetrating arteries
PubMed: 15668448 – two siblings in an African American family with distinctive features of early-onset AD with APP mutations
PMID: 1671712 - V717I mutation identified in 2 unrelated UK families with Alzheimers disease via a genetic linkage study
PMID: 1678058 – 2 individuals from 2 unrelated Japanese families with early onset Alzheimers disease via a genetic linkage study; to: PubMed: 17121991: transgenic mouse study identified that hypoxia increase BACE1 activity which resulted in a significant increase in the production of beta-amyloid in AD-related APP mutations. The study showed that hypoxia up-regulated Bace1 mRNA leading to an increased deposition of beta proteins.

PMID: 1520398 – V717I variant identified in multiple members in a Canadian family of European decent with a dominant inheritance of Alzheimers disease
PMID: 15365148 – 1 family with 6 affected individuals over 3 generations with heterozygous mutations in APP gene – phenotypic features of Alzheimers. Individuals had MRI conducted showing multiple white matter infarcts along the long penetrating arteries
PubMed: 15668448 – two siblings in an African American family with distinctive features of early-onset AD with APP mutations
PMID: 1671712 - V717I mutation identified in 2 unrelated UK families with Alzheimers disease via a genetic linkage study
PMID: 1678058 – 2 individuals from 2 unrelated Japanese families with early onset Alzheimers disease via a genetic linkage study
Incidentalome v0.223 ANG Sangavi Sivagnanasundram reviewed gene: ANG: Rating: GREEN; Mode of pathogenicity: None; Publications: 17886298, 16501576, 18087731, 20301623; Phenotypes: Amyotrophic Lateral Sclerosis (MONDO: 0012753, MIM#611895); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.223 ATP7B Sangavi Sivagnanasundram changed review comment from: Well established gene known to be causative of Wilson Disease (Gene Reviews: NBK1512); Loss of function is a well established mechanism - functional study showed impaired production of copper transport and abberant cellular localization of mutant ATP7B proteins – PMID: 16133174; to: Well established gene known to be causative of Wilson Disease (Gene Reviews: NBK1512); Loss of function is a well established mechanism - functional study showed impaired production of copper transport and abberant cellular localization of mutant ATP7B proteins – PMID: 16133174
Incidentalome v0.223 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related to Spastic paraplegia 79A, autosomal dominant, MIM# 620221; Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Incidentalome v0.222 UCHL1 Zornitza Stark edited their review of gene: UCHL1: Changed phenotypes: Spastic paraplegia 79A, autosomal dominant, MIM# 620221, Spastic paraplegia 79, autosomal recessive, MIM# 615491, MONDO:0014209, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.222 CHEK2 Seb Lunke Phenotypes for gene: CHEK2 were changed from Li-Fraumeni syndrome 2 (MIM#609265); {Breast cancer, susceptibility to} (MIM#114480); {Colorectal cancer, susceptibility to} (MIM#114500); {Prostate cancer, familial, susceptibility to} (MIM#176807) to Li-Fraumeni syndrome 2 (MIM#609265); {Breast cancer, susceptibility to} (MIM#114480); {Colorectal cancer, susceptibility to} (MIM#114500); {Prostate cancer, familial, susceptibility to} (MIM#176807)
Incidentalome v0.221 CHEK2 Seb Lunke Phenotypes for gene: CHEK2 were changed from Breast cancer to Li-Fraumeni syndrome 2 (MIM#609265); {Breast cancer, susceptibility to} (MIM#114480); {Colorectal cancer, susceptibility to} (MIM#114500); {Prostate cancer, familial, susceptibility to} (MIM#176807)
Incidentalome v0.221 CHEK2 Zornitza Stark Mode of inheritance for gene: CHEK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.220 CHEK2 Seb Lunke Mode of inheritance for gene: CHEK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.220 CHEK2 Zornitza Stark Mode of inheritance for gene: CHEK2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.217 UCHL1 Zornitza Stark Phenotypes for gene: UCHL1 were changed from to Spastic paraplegia 79, autosomal recessive, MIM# 615491; MONDO:0014209; Neurodegenerative disease, MONDO:0005559, UCHL1-related
Incidentalome v0.216 UCHL1 Zornitza Stark Mode of inheritance for gene: UCHL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.215 APC Zornitza Stark Phenotypes for gene: APC were changed from to Adenomatous polyposis coli, MIM# 175100
Incidentalome v0.214 APC Zornitza Stark Mode of inheritance for gene: APC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.213 A2M Zornitza Stark Phenotypes for gene: A2M were changed from to Alzheimer disease, MONDO:0004975
Incidentalome v0.212 A2M Zornitza Stark Mode of inheritance for gene: A2M was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.210 GPD1L Zornitza Stark edited their review of gene: GPD1L: Changed rating: RED
Incidentalome v0.210 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Incidentalome v0.208 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.206 SNTA1 Zornitza Stark Phenotypes for gene: SNTA1 were changed from to Long QT syndrome 12, MIM# 612955
Incidentalome v0.204 SNTA1 Zornitza Stark Mode of inheritance for gene: SNTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.202 SCN4B Zornitza Stark Phenotypes for gene: SCN4B were changed from to Long QT syndrome 10, MIM# 611819
Incidentalome v0.200 SCN4B Zornitza Stark Mode of inheritance for gene: SCN4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.198 KCNE2 Zornitza Stark Phenotypes for gene: KCNE2 were changed from to Long QT syndrome 6, MIM# 613693
Incidentalome v0.196 KCNE2 Zornitza Stark Mode of inheritance for gene: KCNE2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.194 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from to Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Long QT syndrome 5, MIM# 613695
Incidentalome v0.193 KCNE1 Zornitza Stark Mode of inheritance for gene: KCNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.192 KCNE1 Zornitza Stark edited their review of gene: KCNE1: Changed rating: GREEN; Changed phenotypes: Jervell and Lange-Nielsen syndrome 2, MIM# 612347, Long QT syndrome 5, MIM# 613695; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.191 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from to Long QT syndrome 1, MIM# 192500; Short QT syndrome 2, MIM# 609621; Jervell and Lange-Nielsen syndrome, MIM# 220400; Atrial fibrillation, familial, 3, MIM# 607554
Incidentalome v0.190 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.189 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 1, MIM# 192500, Short QT syndrome 2, MIM# 609621, Jervell and Lange-Nielsen syndrome, MIM# 220400, Atrial fibrillation, familial, 3, MIM# 607554; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.189 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from to Long QT syndrome 2, MIM# 613688; Short QT syndrome , MIM#1 609620
Incidentalome v0.187 KCNH2 Zornitza Stark Mode of inheritance for gene: KCNH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.186 CACNB2 Zornitza Stark Phenotypes for gene: CACNB2 were changed from to Brugada syndrome 4, MIM# 611876
Incidentalome v0.184 CACNB2 Zornitza Stark Mode of inheritance for gene: CACNB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.182 PRKAG2 Zornitza Stark Phenotypes for gene: PRKAG2 were changed from to Cardiomyopathy, hypertrophic 6, MIM# 600858; Glycogen storage disease of heart, lethal congenital, MIM# 261740
Incidentalome v0.180 PRKAG2 Zornitza Stark Mode of inheritance for gene: PRKAG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.179 PRKAG2 Zornitza Stark edited their review of gene: PRKAG2: Added comment: Variants associated with cardiomyopathy, conduction disease, and ventricular pre-excitation. More than 50 unrelated individuals reported. Can present with isolated HCM.; Changed publications: 15877279, 17667862, 32646569; Changed phenotypes: Cardiomyopathy, hypertrophic 6, MIM# 600858, Glycogen storage disease of heart, lethal congenital, MIM# 261740
Incidentalome v0.179 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Incidentalome v0.177 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.176 MYL2 Zornitza Stark Phenotypes for gene: MYL2 were changed from to Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, MIM# 619424; Cardiomyopathy, hypertrophic, 10, MIM# 608758
Incidentalome v0.174 MYL2 Zornitza Stark Mode of inheritance for gene: MYL2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.172 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from to Hypertrophic cardiomyopathy; congenital heart defects; conduction abnormalities; Timothy syndrome, MIM# 601005; Long QT syndrome 8, MIM# 618447
Incidentalome v0.170 CACNA1C Zornitza Stark Mode of inheritance for gene: CACNA1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Incidentalome v0.169 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Changed phenotypes: Hypertrophic cardiomyopathy, congenital heart defects, conduction abnormalities, Timothy syndrome, MIM# 601005, Long QT syndrome 8, MIM# 618447
Incidentalome v0.169 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Changed rating: GREEN
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
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
Incidentalome v0.167 TTN Zornitza Stark Mode of inheritance for gene: TTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.166 TTN Zornitza Stark changed review comment from: DEFINITIVE by ClinGen.; to: DEFINITIVE by ClinGen for DCM and myopathy.

MODERATE for tibial muscular dystrophy and myofibrillar myopathy.

LIMITED for HCM and ARVC.
Incidentalome v0.166 TTN Zornitza Stark edited their review of gene: TTN: Changed phenotypes: Cardiomyopathy, dilated, 1G, MIM#604145, Cardiomyopathy, familial hypertrophic, 9, MIM# 613765, Tibial muscular dystrophy, tardive, MIM#600334, Salih myopathy (MIM#611705), Muscular dystrophy, limb-girdle, type 2J, 608807; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.166 TPM1 Zornitza Stark Phenotypes for gene: TPM1 were changed from to Cardiomyopathy, dilated, 1Y, MIM# 611878; Cardiomyopathy, hypertrophic, 3, MIM# 115196
Incidentalome v0.164 TPM1 Zornitza Stark Mode of inheritance for gene: TPM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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.
Incidentalome v0.163 TPM1 Zornitza Stark edited their review of gene: TPM1: Changed phenotypes: Cardiomyopathy, dilated, 1Y, MIM# 611878, Cardiomyopathy, hypertrophic, 3, MIM# 115196; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.163 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from to Cardiomyopathy, dilated, 1D, MIM# 601494; Cardiomyopathy, hypertrophic, 2, MIM# 115195; Cardiomyopathy, familial restrictive, 3, MIM# 612422; Left ventricular noncompaction 6, MIM# 601494
Incidentalome v0.161 TNNT2 Zornitza Stark Mode of inheritance for gene: TNNT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.160 TNNT2 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families, functional data. The p.Lys210del variant is a recurrent pathogenic variant.; to: DEFINITIVE by ClinGen for DCM and HCM, multiple families, functional data. The p.Lys210del variant is a recurrent pathogenic variant.
Incidentalome v0.160 TNNT2 Zornitza Stark edited their review of gene: TNNT2: Changed publications: 33947203, 11106718, 20978592, 20031601, 15542288, 17556660, 30681346; Changed phenotypes: Cardiomyopathy, dilated, 1D, MIM# 601494, Cardiomyopathy, hypertrophic, 2, MIM# 115195, Cardiomyopathy, familial restrictive, 3, MIM# 612422, Left ventricular noncompaction 6, MIM# 601494
Incidentalome v0.160 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from to Cardiomyopathy, dilated, 1FF, MIM#613286; Cardiomyopathy, hypertrophic, 7, MIM# 613690; Cardiomyopathy, familial restrictive, MIM#1115210
Incidentalome v0.158 TNNI3 Zornitza Stark Mode of inheritance for gene: TNNI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.157 TNNI3 Zornitza Stark edited their review of gene: TNNI3: Changed publications: 22464770, 31568572, 19590045, 20215591, 21846512, 2226790, 30681346; Changed phenotypes: Cardiomyopathy, dilated, 1FF, MIM#613286, Cardiomyopathy, hypertrophic, 7, MIM# 613690
Incidentalome v0.157 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from to Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900; Cardiomyopathy, dilated, 1E, MIM# 601154
Incidentalome v0.155 SCN5A Zornitza Stark edited their review of gene: SCN5A: Added comment: Variants in this gene are also associated with a range of arrhythmia disorders.; Changed phenotypes: Long QT syndrome 3 (MIM#603830), Sick sinus syndrome 1, MIM# 608567, Ventricular fibrillation, familial, 1, MIM# 603829, Brugada syndrome 1, MIM# 601144, Heart block, progressive, type IA, MIM# 113900
Incidentalome v0.155 SCN5A Zornitza Stark Mode of inheritance for gene: SCN5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.154 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from to Cardiomyopathy, dilated, 1S, MIM# 613426; MONDO:0013262; Cardiomyopathy, hypertrophic, 1, MIM# 192600; Laing distal myopathy, MIM# 160500; Myopathy, myosin storage, autosomal dominant, MIM# 608358; Myopathy, myosin storage, autosomal recessive, MIM# 255160
Incidentalome v0.152 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.151 MYH7 Zornitza Stark edited their review of gene: MYH7: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.151 MYH7 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families with segregation evidence and functional data.; to: DEFINITIVE by ClinGen for HCM and DCM, multiple families with segregation evidence and functional data.

Also multiple families reported with skeletal myopathies.
Incidentalome v0.151 MYH7 Zornitza Stark edited their review of gene: MYH7: Changed publications: 21483645, 30874888, 21846512, 30384889, 25935763, 24558114, 27000522, 31179125, 24119082, 27965028, 33947203, 30681346, 15322983; Changed phenotypes: Cardiomyopathy, dilated, 1S, MIM# 613426, MONDO:0013262, Cardiomyopathy, hypertrophic, 1, MIM# 192600, Laing distal myopathy, MIM# 160500, Myopathy, myosin storage, autosomal dominant, MIM# 608358, Myopathy, myosin storage, autosomal recessive, MIM# 255160
Incidentalome v0.151 MYBPC3 Zornitza Stark Phenotypes for gene: MYBPC3 were changed from to Cardiomyopathy, dilated, 1MM, MIM#615396; Cardiomyopathy, hypertrophic, 4, MIM# 115197
Incidentalome v0.150 MYBPC3 Zornitza Stark Mode of inheritance for gene: MYBPC3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.149 MYBPC3 Zornitza Stark changed review comment from: Association with HCM is definitive.

No segregation or experimental data to support association with DCM. VOUS only in large cohorts.; to: Association with HCM is DEFINITIVE.

No segregation or experimental data to support association with DCM. VOUS only in large cohorts.
Incidentalome v0.149 MYBPC3 Zornitza Stark edited their review of gene: MYBPC3: Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, dilated, 1MM, MIM#615396, Cardiomyopathy, hypertrophic, 4, MIM# 115197; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.149 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Cardiomyopathy, dilated, 1R, MIM# 613424; Cardiomyopathy, hypertrophic, 11, MIM# 612098; Atrial septal defect 5, MIM# 612794
Incidentalome v0.147 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.146 ACTC1 Zornitza Stark edited their review of gene: ACTC1: Added comment: LIMITED to MODERATE association with congenital heart disease.; Changed publications: 31430208, 30384889, 9563954, 14605248, 20600154, 26432839, 17947298, 31430208; Changed phenotypes: Cardiomyopathy, dilated, 1R, MIM# 613424, Cardiomyopathy, hypertrophic, 11, MIM# 612098, Atrial septal defect 5, MIM# 612794
Incidentalome v0.145 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from to Arrhythmogenic right ventricular dysplasia 5, MIM# 604400; Auditory neuropathy, autosomal dominant 3, MIM# 619832; Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Incidentalome v0.143 TMEM43 Zornitza Stark Mode of inheritance for gene: TMEM43 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.142 TMEM43 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen, multiple families reported, functional data. Common founder variant p.Ser358Leu.; to: DEFINITIVE by ClinGen for ARVC, multiple families reported, functional data. Common founder variant p.Ser358Leu.
Incidentalome v0.142 TMEM43 Zornitza Stark edited their review of gene: TMEM43: Added comment: Association with deafness: MODERATE, two multiplex families with missense variants.

Association with muscular dystrophy LIMITED to MODERATE:
PMID: 21391237 (2011): Different variants reported in 2 adults with EDMD-related myopathy. Ile91Val present in gnomad, 20 hets. Other variant, Glu85Lys, presented in gnomad (1 het)

PMID: 30311943 (2019): 1 EDMD family reported with the same Glu85Lys variant. Muscle disease suspected at age of 17 in one family member.; Changed publications: 18313022, 21214875, 23812740, 22725725, 24598986, 29980933, 34050020, 21391237, 30311943; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM# 604400, Auditory neuropathy, autosomal dominant 3, MIM# 619832, Emery-Dreifuss muscular dystrophy 7 (MIM#614302)
Incidentalome v0.142 RYR2 Zornitza Stark Phenotypes for gene: RYR2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772; Arrhythmogenic right ventricular dysplasia 2, MIM# 600996; Hypertrophic cardiomyopathy
Incidentalome v0.140 RYR2 Zornitza Stark Mode of inheritance for gene: RYR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.139 RYR2 Zornitza Stark changed review comment from: Gene-disease association assessed as REFUTED by ClinGen: 57 papers reviewed in the process. Some of the original variants were relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis was not provided, segregation information was not informative and/or CPVT was also present in the family. In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670).; to: ARVC: gene-disease association assessed as REFUTED by ClinGen: 57 papers reviewed in the process. Some of the original variants were relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis was not provided, segregation information was not informative and/or CPVT was also present in the family. In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670).
Incidentalome v0.139 RYR2 Zornitza Stark edited their review of gene: RYR2: Added comment: DEFINITVE for CPVT.

REFUTED for ARVC.

LIMITED for HCM.; Changed rating: GREEN; Changed publications: 11159936, 25041964, 29543670, 11208676, 12093772; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772, Arrhythmogenic right ventricular dysplasia 2, MIM# 600996, Hypertrophic cardiomyopathy
Incidentalome v0.139 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
Incidentalome v0.137 PKP2 Zornitza Stark Mode of inheritance for gene: PKP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.136 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from to Cardiomyopathy, dilated, 1A, MIM# 115200; Arrhythmogenic right ventricular cardiomyopathy; Lipodystrophy, familial partial, type 2, MIM# 151660; Emery-Dreifuss muscular dystrophy 2, MIM#181350; Mandibuloacral dysplasia 248370; Restrictive dermopathy, lethal 275210; Hutchinson-Gilford progeria 176670; Muscular dystrophy, congenital 613205
Incidentalome v0.134 LMNA Zornitza Stark Mode of inheritance for gene: LMNA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.133 LMNA Zornitza Stark edited their review of gene: LMNA: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.133 LMNA Zornitza Stark Mode of inheritance for gene: LMNA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.132 LMNA Zornitza Stark changed review comment from: Association between LMNA and ARVC has been rated as LIMITED by ClinGen: small number of families reported where only some of the individuals with the variants had convincing ARVC phenotype. Rated Amber on this panel more due to phenotypic overlap with DCM and arrhythmias arising in this context.
Sources: Expert list; to: Established association with multiple phenotypes.
Incidentalome v0.132 LMNA Zornitza Stark edited their review of gene: LMNA: Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, dilated, 1A, MIM# 115200, Arrhythmogenic right ventricular cardiomyopathy, Lipodystrophy, familial partial, type 2, MIM# 151660, Emery-Dreifuss muscular dystrophy 2, MIM#181350, Mandibuloacral dysplasia 248370, Restrictive dermopathy, lethal 275210, Hutchinson-Gilford progeria 176670, Muscular dystrophy, congenital 613205
Incidentalome v0.132 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic, MIM# 609638
Incidentalome v0.130 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.129 DSP Zornitza Stark edited their review of gene: DSP: Added comment: Established gene-disease associations.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450, Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821, Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676, Epidermolysis bullosa, lethal acantholytic, MIM# 609638
Incidentalome v0.129 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193; Cardiomyopathy, dilated, 1BB, MIM# 612877
Incidentalome v0.127 DSG2 Zornitza Stark Mode of inheritance for gene: DSG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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
Incidentalome v0.126 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Incidentalome v0.124 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.122 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from to Loeys-Dietz syndrome 2 , MIM#610168
Incidentalome v0.120 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.119 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from to Loeys-Dietz syndrome 1, MIM# 609192
Incidentalome v0.117 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.115 MYLK Zornitza Stark Phenotypes for gene: MYLK were changed from to Aortic aneurysm, familial thoracic 7, MIM#613780; Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#249210
Incidentalome v0.113 MYLK Zornitza Stark Mode of inheritance for gene: MYLK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.112 MYLK Zornitza Stark edited their review of gene: MYLK: Changed publications: 28602422
Incidentalome v0.112 MYLK Zornitza Stark edited their review of gene: MYLK: Added comment: Amber for bi-allelic variants and gastrointestinal neuromuscular disease:
PMID: 28602422;
- 3 affecteds from 2 consanguineous families. each family is homozygous for 1x fs and 1x splice (abnormal splicing proven).
- IHC of 1 affected showed no protein expression in intestine and bladder
- For both families, no cardiac problems were reported for the carrier parents.; Changed phenotypes: Aortic aneurysm, familial thoracic 7, MIM#613780, Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#249210; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.112 MYH11 Zornitza Stark Phenotypes for gene: MYH11 were changed from to Visceral myopathy 2, MIM# 619350; Megacystis microcolon intestinal hypoperistalsis syndrome, autosomal recessive, MIM#619351; Aortic aneurysm, familial thoracic 4, MIM# 132900
Incidentalome v0.110 MYH11 Zornitza Stark Mode of inheritance for gene: MYH11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.109 HCN4 Zornitza Stark Phenotypes for gene: HCN4 were changed from to Sick sinus syndrome 2, MIM# 163800; Aortopathy
Incidentalome v0.107 HCN4 Zornitza Stark Mode of inheritance for gene: HCN4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.106 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Acromicric dysplasia (102370); Ectopia lentis, familial (129600); Geleophysic dysplasia 2 (614185); Marfan lipodystrophy syndrome (616914); Marfan syndrome (154700); MASS syndrome (604308); Stiff skin syndrome (184900); Weill-Marchesani syndrome 2, dominant (608328)
Incidentalome v0.104 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.103 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Ehlers-Danlos syndrome, vascular type, MIM# 130050; Polymicrogyria with or without vascular-type EDS, MIM# 618343
Incidentalome v0.101 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.100 BGN Zornitza Stark Phenotypes for gene: BGN were changed from to Meester-Loeys syndrome, MIM# 300989; Spondyloepimetaphyseal dysplasia, X-linked, MIM# 300106
Incidentalome v0.98 BGN Zornitza Stark Mode of inheritance for gene: BGN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.97 BGN Zornitza Stark edited their review of gene: BGN: Changed rating: GREEN; Changed phenotypes: Meester-Loeys syndrome, MIM# 300989, Spondyloepimetaphyseal dysplasia, X-linked, MIM# 300106; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.96 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from to Aortic aneurysm, familial thoracic 6, MIM# 611788; Multisystemic smooth muscle dysfunction syndrome, MIM# 613834
Incidentalome v0.94 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.91 MBD4 Alison Yeung Phenotypes for gene: MBD4 were changed from AML and colorectal polyps; MBD4-associated neoplasia syndrome to Hereditary neoplastic syndrome, MBD4-associated MONDO:0015356
Incidentalome v0.90 MBD4 Chern Lim edited their review of gene: MBD4: Added comment: PMID:35460607: Biallelic loss-of-function germline variants in four families with five individuals with adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma.

PMID:35381620: A 37-year-old man presented with symptomatic anaemia and pancytopenia, a diagnosis of myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia (MDS-RS-MLD) was made on bone marrow biopsy, patient has a homozygous missense variant in the germline.; Changed rating: GREEN
Incidentalome v0.88 THSD4 Zornitza Stark Phenotypes for gene: THSD4 were changed from Thoracic aortic aneurysm and dissection (TAAD) to Aortic aneurysm, familial thoracic 12, MIM# 619825
Incidentalome v0.87 THSD4 Zornitza Stark edited their review of gene: THSD4: Changed phenotypes: Aortic aneurysm, familial thoracic 12, MIM# 619825
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 v0.83 WT1 Seb Lunke Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome, MIM# 194080; Frasier syndrome, MIM#136680; Wilms tumor, type 1, MIM#194070; Nephrotic syndrome, type 4, MIM#256370
Incidentalome v0.82 WT1 Seb Lunke Mode of inheritance for gene: WT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.81 CACNA2D1 Zornitza Stark Mode of inheritance for gene: CACNA2D1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.75 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from to Long QT syndrome 4, MIM# 600919
Incidentalome v0.73 ANK2 Zornitza Stark Mode of inheritance for gene: ANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.65 HTT Zornitza Stark Phenotypes for gene: HTT were changed from to Huntington disease, MIM# 143100
Incidentalome v0.63 HTT Zornitza Stark Mode of inheritance for gene: HTT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.62 HTT Eleanor Williams changed review comment from: PMID: 33432339 - Jung et al 2021 - further characterisation of the family previously reported in PMID: 27329733 (Rodan et al 2016) - using WGS they confirm they are the most likely cause of the LOMARS phenotype and clarify their locations as NM_002111.8(HTT): c.8157T>A (p.Phe2719Leu) and NM_002111.8(HTT)c.4469+1G>A (Note there are incorrect Clinvar entries). Functional studies show them each to be a hypomorphic mutation, resulting in severe deficiency of huntingtin in compound heterozygotes.

Still only 2 cases reported to date with biallelic LOF variants in HTT associated with the LOMARS phenotype although this study add further weight with some functional data.; to: PMID: 33432339 - Jung et al 2021 - further characterisation of the family previously reported in PMID: 27329733 (Rodan et al 2016) - using WGS they confirm they are the most likely cause of the LOMARS phenotype and clarify their locations as NM_002111.8(HTT): c.8157T>A (p.Phe2719Leu) and NM_002111.8(HTT)c.4469+1G>A (Note there are incorrect Clinvar entries). Functional studies show them each to be a hypomorphic mutation, resulting in severe deficiency of huntingtin in compound heterozygotes.

Still only 2 cases reported to date ((PMID: 27329733/33432339 and 26740508) with biallelic LOF variants in HTT associated with the LOMARS phenotype although this study add further weight with some functional data.
Incidentalome v0.62 UQCRC1 Zornitza Stark Phenotypes for gene: UQCRC1 were changed from Parkinson's disease to Parkinsonism with polyneuropathy, MIM# 619279
Incidentalome v0.61 UQCRC1 Zornitza Stark edited their review of gene: UQCRC1: Changed phenotypes: Parkinsonism with polyneuropathy, MIM# 619279
Incidentalome v0.57 CCNF Zornitza Stark Phenotypes for gene: CCNF were changed from amyotrophic lateral sclerosis with/without frontotemporal dementia to Frontotemporal dementia and/or amyotrophic lateral sclerosis 5, MIM# 619141
Incidentalome v0.54 NF2 Zornitza Stark Phenotypes for gene: NF2 were changed from to Neurofibromatosis, type 2, MIM# 101000
Incidentalome v0.52 NF2 Zornitza Stark Mode of inheritance for gene: NF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.51 SNCA Zornitza Stark Phenotypes for gene: SNCA were changed from to Dementia, Lewy body (MIM#127750); Parkinson disease 1 (MIM#168601); Parkinson disease 4 (MIM#605543)
Incidentalome v0.49 SNCA Zornitza Stark Mode of inheritance for gene: SNCA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Incidentalome v0.47 GLA Zornitza Stark Phenotypes for gene: GLA were changed from to Fabry disease 301500; Fabry disease, cardiac variant 301500
Incidentalome v0.45 GLA Zornitza Stark Mode of pathogenicity for gene: GLA was changed from to Other
Incidentalome v0.44 GLA Zornitza Stark Mode of inheritance for gene: GLA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Incidentalome v0.43 TUBA4A Zornitza Stark Phenotypes for gene: TUBA4A were changed from to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208
Incidentalome v0.41 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.39 SNCB Zornitza Stark Phenotypes for gene: SNCB were changed from to Dementia, Lewy body, MIM#127750
Incidentalome v0.37 SNCB Zornitza Stark Mode of inheritance for gene: SNCB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.31 AKAP9 Zornitza Stark Phenotypes for gene: AKAP9 were changed from to Long QT syndrome 11, MIM# 611820
Incidentalome v0.29 AKAP9 Zornitza Stark Mode of inheritance for gene: AKAP9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.24 GPD1L Zornitza Stark Phenotypes for gene: GPD1L were changed from to Brugada syndrome 2, MIM# 611777
Incidentalome v0.22 GPD1L Zornitza Stark Mode of inheritance for gene: GPD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.19 SMAD3 Zornitza Stark Phenotypes for gene: SMAD3 were changed from to Loeys-Dietz syndrome 3, MIM# 613795
Incidentalome v0.17 SMAD3 Zornitza Stark Mode of inheritance for gene: SMAD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.8 DDX41 Zornitza Stark gene: DDX41 was added
gene: DDX41 was added to Incidentalome. Sources: Expert list
Mode of inheritance for gene: DDX41 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDX41 were set to {Myeloproliferative/lymphoproliferative neoplasms, familial (multiple types), susceptibility to} MIM# 616871
Review for gene: DDX41 was set to GREEN
Added comment: Adult-onset disorder, often initially presents with myelodysplasia +/- a range of haematological malignancies. Reduced penetrance.
Sources: Expert list
Incidentalome v0.7 Zornitza Stark Panel name changed from Incidentalome_VCGS to Incidentalome
Panel types changed to Victorian Clinical Genetics Services
Incidentalome v0.0 ANG Zornitza Stark gene: ANG was added
gene: ANG was added to Incidentalome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ANG was set to Unknown