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Genomic screening in children: BabyScreen+ v0.99 PCSK9 Zornitza Stark Tag cardiac tag was added to gene: PCSK9.
Tag treatable tag was added to gene: PCSK9.
Genomic screening in children: BabyScreen+ v0.98 Zornitza Stark Panel status changed from internal to public
Genomic screening in children: BabyScreen+ v0.97 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.96 JUP Zornitza Stark edited their review of gene: JUP: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.96 CEL Seb Lunke Mode of pathogenicity for gene: CEL was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genomic screening in children: BabyScreen+ v0.95 CEL Seb Lunke Added comment: Comment on mode of pathogenicity: Dominant Negative Gain-of-Function experimentally established
Genomic screening in children: BabyScreen+ v0.95 CEL Seb Lunke Mode of pathogenicity for gene: CEL was changed from Other to Other
Genomic screening in children: BabyScreen+ v0.94 CEL Seb Lunke Mode of pathogenicity for gene: CEL was changed from to Other
Genomic screening in children: BabyScreen+ v0.93 CEL Seb Lunke Marked gene: CEL as ready
Genomic screening in children: BabyScreen+ v0.93 CEL Seb Lunke Gene: cel has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.93 CEL Seb Lunke Publications for gene: CEL were set to 24062244; 21784842; 19760265; 18544793; 17989309; 16369531; 29233499; 27650499
Genomic screening in children: BabyScreen+ v0.92 CEL Seb Lunke changed review comment from: Specific CEL gene variants have been associated with MODY8, and potentially hereditary chronic pancreatitis, in 5 families to date (PMID:37726640). All families have single base frame shift deletions in the VNTR (Variable Number of Tandem Repeats) region of the last exon (exon 11) of the CEL gene, specifically in the first (DEL1), fourth and fifth (DEL4,5) repeat of the VNTR region (GRCh38 chr9:133,071,168-133,071,332).

Experimental evidence supports a Gain of Function, dominant negative mechanism of pathogenicity, in which certain frameshift variants cause the resulting protein to from toxic cellular aggregates (29233499). Crucially, an extended number of frameshifted repeats seem to be required to facilitate the formation of these aggregates (27650499, 38483348, 33862081). This is likely due to the increased presence of cysteine residues facilitating di-sulphide bonds, and the decreased presence of Threonine residuce that undergo O-glycosylation which is necessary for protein secretion. In addition, heterozygous NMD variants are common in gnomAD v4 for this gene, further arguing against dominant LoF as a pathogenic mechanism despite the potential for late onset and reduced penetrance.

Importantly, both more distal frameshift deletions, distal single base insertions (beyond repeat 7), and frameshift variants that result in a premature termination codon in the same repeat, have no strong evidence for pathogenicity to date as they do not result in toxic protein aggregation (38483348, 33862081). Some insertions in the proximal VNTR region, in particular in the first and fourth repeat (INS1, INS4), may confer an increased risk of pancreatitis, but evidence so far remains inconclusive (PMID:38483348). More distal single base insertions (beyond repeat 7) and distal deletions have been described as likely benign.

From a technical perspective, the region is challenging to map for short read NGS technologies due to the repetitive nature and high GC content. At least the five four repeats critical for MODY however are reasonably well covered in srWGS and WES data, and should be callable in routine testing. Although the fifth repeat does have increasing numbers of multimapping reads which may start to reduce sensitivity.; to: Specific CEL gene variants have been associated with MODY8, and potentially hereditary chronic pancreatitis, in 5 families to date (PMID:37726640). All families have single base frame shift deletions in the VNTR (Variable Number of Tandem Repeats) region of the last exon (exon 11) of the CEL gene, specifically in the first (DEL1), fourth and fifth (DEL4,5) repeat of the VNTR region (GRCh38 chr9:133,071,168-133,071,332).

Experimental evidence supports a Gain of Function, dominant negative mechanism of pathogenicity, in which certain frameshift variants cause the resulting protein to from toxic cellular aggregates (29233499). Crucially, an extended number of frameshifted repeats seem to be required to facilitate the formation of these aggregates (27650499, 38483348, 33862081). This is likely due to the increased presence of cysteine residues facilitating di-sulphide bonds, and the decreased presence of Threonine residuce that undergo O-glycosylation which is necessary for protein secretion. In addition, heterozygous NMD variants are common in gnomAD v4 for this gene (pLI = 0, o/e = 0.74), further arguing against dominant LoF as a pathogenic mechanism despite the potential for late onset and reduced penetrance.

Importantly, both more distal frameshift deletions, distal single base insertions (beyond repeat 7), and frameshift variants that result in a premature termination codon in the same repeat, have no strong evidence for pathogenicity to date as they do not result in toxic protein aggregation (38483348, 33862081). Some insertions in the proximal VNTR region, in particular in the first and fourth repeat (INS1, INS4), may confer an increased risk of pancreatitis, but evidence so far remains inconclusive (PMID:38483348). More distal single base insertions (beyond repeat 7) and distal deletions have been described as likely benign.

From a technical perspective, the region is challenging to map for short read NGS technologies due to the repetitive nature and high GC content. At least the five four repeats critical for MODY however are reasonably well covered in srWGS and WES data, and should be callable in routine testing. Although the fifth repeat does have increasing numbers of multimapping reads which may start to reduce sensitivity.
Genomic screening in children: BabyScreen+ v0.92 CEL Seb Lunke changed review comment from: Specific CEL gene variants have been associated with MODY8, and potentially hereditary chronic pancreatitis, in 5 families to date (PMID:37726640). All families have single base frame shift deletions in the VNTR (Variable Number of Tandem Repeats) region of the last exon (exon 11) of the CEL gene, specifically in the first (DEL1), fourth and fifth (DEL4,5) repeat of the VNTR region (GRCh38 chr9:133,071,168-133,071,332).

Experimental evidence supports a Gain of Function, dominant negative mechanism of pathogenicity, in which certain frameshift variants cause the resulting protein to from toxic cellular aggregates (29233499). Crucially, an extended number of frameshifted repeats seem to be required to facilitate the formation of these aggregates (27650499, 38483348, 33862081). This is likely due to the increased presence of cysteine residues facilitating di-sulphide bonds, and the decreased presence of Threonine residuce that undergo O-glycosylation which is necessary for protein secretion.

Importantly, both more distal frameshift deletions, distal single base insertions (beyond repeat 7), and frameshift variants that result in a premature termination codon in the same repeat, have no strong evidence for pathogenicity to date as they do not result in toxic protein aggregation (38483348, 33862081). Some insertions in the proximal VNTR region, in particular in the first and fourth repeat (INS1, INS4), may confer an increased risk of pancreatitis, but evidence so far remains inconclusive (PMID:38483348). More distal single base insertions (beyond repeat 7) and distal deletions have been described as likely benign.

From a technical perspective, the region is challenging to map for short read NGS technologies due to the repetitive nature and high GC content. At least the five four repeats critical for MODY however are reasonably well covered in srWGS and WES data, and should be callable in routine testing. Although the fifth repeat does have increasing numbers of multimapping reads which may start to reduce sensitivity.; to: Specific CEL gene variants have been associated with MODY8, and potentially hereditary chronic pancreatitis, in 5 families to date (PMID:37726640). All families have single base frame shift deletions in the VNTR (Variable Number of Tandem Repeats) region of the last exon (exon 11) of the CEL gene, specifically in the first (DEL1), fourth and fifth (DEL4,5) repeat of the VNTR region (GRCh38 chr9:133,071,168-133,071,332).

Experimental evidence supports a Gain of Function, dominant negative mechanism of pathogenicity, in which certain frameshift variants cause the resulting protein to from toxic cellular aggregates (29233499). Crucially, an extended number of frameshifted repeats seem to be required to facilitate the formation of these aggregates (27650499, 38483348, 33862081). This is likely due to the increased presence of cysteine residues facilitating di-sulphide bonds, and the decreased presence of Threonine residuce that undergo O-glycosylation which is necessary for protein secretion. In addition, heterozygous NMD variants are common in gnomAD v4 for this gene, further arguing against dominant LoF as a pathogenic mechanism despite the potential for late onset and reduced penetrance.

Importantly, both more distal frameshift deletions, distal single base insertions (beyond repeat 7), and frameshift variants that result in a premature termination codon in the same repeat, have no strong evidence for pathogenicity to date as they do not result in toxic protein aggregation (38483348, 33862081). Some insertions in the proximal VNTR region, in particular in the first and fourth repeat (INS1, INS4), may confer an increased risk of pancreatitis, but evidence so far remains inconclusive (PMID:38483348). More distal single base insertions (beyond repeat 7) and distal deletions have been described as likely benign.

From a technical perspective, the region is challenging to map for short read NGS technologies due to the repetitive nature and high GC content. At least the five four repeats critical for MODY however are reasonably well covered in srWGS and WES data, and should be callable in routine testing. Although the fifth repeat does have increasing numbers of multimapping reads which may start to reduce sensitivity.
Genomic screening in children: BabyScreen+ v0.92 CEL Seb Lunke reviewed gene: CEL: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27650499, 29233499, 33862081, 37726640, 38483348; Phenotypes: Maturity-onset diabetes of the young, type VIII, MIM#609812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.92 NF2 Lilian Rudd gene: NF2 was added
gene: NF2 was added to Genomic screening in children: BabyScreen+. Sources: Expert List
cancer tags were added to gene: NF2.
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF2 were set to Schwannomatosis, vestibular MIM#101000
Review for gene: NF2 was set to GREEN
Added comment: EviQ guideline:
From infancy
Annual neurological examination3
Annual speech and pure tone audiology with auditory brainstem evoked potentials3, 4
From 10-20 years
Annual cranial and spinal MRI with gadolinium enhancement (gold standard)3, 4
Once tumours are present, MRI screening should be at least annual until the individual growth rate is established.3 The ongoing interval for follow-up imaging of tumours is dependent on tumour location and growth rate3, 4
Sources: Expert List
Genomic screening in children: BabyScreen+ v0.91 NEUROD1 Zornitza Stark Tag treatable tag was added to gene: NEUROD1.
Tag endocrine tag was added to gene: NEUROD1.
Genomic screening in children: BabyScreen+ v0.91 LDLRAP1 Zornitza Stark Tag cardiac tag was added to gene: LDLRAP1.
Tag treatable tag was added to gene: LDLRAP1.
Genomic screening in children: BabyScreen+ v0.91 LDLR Zornitza Stark Tag cardiac tag was added to gene: LDLR.
Tag treatable tag was added to gene: LDLR.
Genomic screening in children: BabyScreen+ v0.91 KCNJ11 Zornitza Stark Tag treatable tag was added to gene: KCNJ11.
Tag endocrine tag was added to gene: KCNJ11.
Genomic screening in children: BabyScreen+ v0.91 CDC73 Lilian Rudd gene: CDC73 was added
gene: CDC73 was added to Genomic screening in children: BabyScreen+. Sources: Expert List
Mode of inheritance for gene: CDC73 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDC73 were set to Hyperparathyroidism-jaw tumor syndrome MIM#145001
Review for gene: CDC73 was set to GREEN
Added comment: EviQ guideline:
From age 10 years
Annual fasting calcium, phosphate, vitamin D and parathyroid hormone
Annual clinical examination of the neck
Sources: Expert List
Genomic screening in children: BabyScreen+ v0.88 AIP Lilian Rudd gene: AIP was added
gene: AIP was added to Genomic screening in children: BabyScreen+. Sources: Expert List
Mode of inheritance for gene: AIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: AIP were set to Pituitary adenoma predisposition MIM#102200
Review for gene: AIP was set to GREEN
Added comment: EVIQ screening guideline:
From age 10 years
Annual history and clinical examination
Annual visual field testing by confrontation*
Annual biochemical assessment with prolactin and IGF-1
Baseline high resolution pituitary MRI. Repeat every 5 years
Sources: Expert List
Genomic screening in children: BabyScreen+ v0.86 APC Lilian Rudd gene: APC was added
gene: APC was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
cancer tags were added to gene: APC.
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: APC were set to Adenomatous polyposis coli MIM#175100
Review for gene: APC was set to GREEN
Added comment: high lifetime risk of cancer
screening recommendation from age 10
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.85 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Genomic screening in children: BabyScreen+ v0.85 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.85 KCNJ11 Zornitza Stark Classified gene: KCNJ11 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.85 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.84 KCNJ11 Zornitza Stark gene: KCNJ11 was added
gene: KCNJ11 was added to Genomic screening in children: BabyScreen+. Sources: Literature
Mode of inheritance for gene: KCNJ11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ11 were set to 32027066; 32376986
Phenotypes for gene: KCNJ11 were set to Monogenic diabetes MONDO:0015967, KCNJ11-related
Review for gene: KCNJ11 was set to GREEN
Added comment: DEFINITIVE by ClinGen.

The usual mechanism for disease is heterozygous gain of function.

Note multiple disease entities are associated with variants in this gene. The ClinGen Lumping and Splitting Working Group has split curations for these disease entities. The following entities have been lumped under (1) autosomal dominant monogenic diabetes, which presents as three phenotypic disease sub-entities: (1A) Permanent neonatal diabetes mellitus, (MIM:606176), (1B) Transient neonatal diabetes, 3 (MIM:125853), and less commonly, (1C) Maturity-onset diabetes of the young, type 13 (MODY13) (MIM:616329).

These have been split from (2) hyperinsulinaemic hypoglycaemia, familial, 2 (MIM:601820).
Sources: Literature
Genomic screening in children: BabyScreen+ v0.83 INS Zornitza Stark Tag treatable tag was added to gene: INS.
Tag endocrine tag was added to gene: INS.
Genomic screening in children: BabyScreen+ v0.83 HNF4A Zornitza Stark Tag treatable tag was added to gene: HNF4A.
Tag endocrine tag was added to gene: HNF4A.
Genomic screening in children: BabyScreen+ v0.83 HNF1B Zornitza Stark Tag cnv was removed from gene: HNF1B.
Tag SV/CNV tag was added to gene: HNF1B.
Tag treatable tag was added to gene: HNF1B.
Tag endocrine tag was added to gene: HNF1B.
Genomic screening in children: BabyScreen+ v0.83 GCK Zornitza Stark Tag treatable tag was added to gene: GCK.
Tag endocrine tag was added to gene: GCK.
Genomic screening in children: BabyScreen+ v0.83 CEL Zornitza Stark Tag treatable tag was added to gene: CEL.
Tag endocrine tag was added to gene: CEL.
Genomic screening in children: BabyScreen+ v0.83 APOB Zornitza Stark Tag cardiac tag was added to gene: APOB.
Genomic screening in children: BabyScreen+ v0.83 ABCC8 Zornitza Stark Tag treatable tag was added to gene: ABCC8.
Tag endocrine tag was added to gene: ABCC8.
Genomic screening in children: BabyScreen+ v0.83 LDLR Zornitza Stark Marked gene: LDLR as ready
Genomic screening in children: BabyScreen+ v0.83 LDLR Zornitza Stark Gene: ldlr has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.83 LDLR Zornitza Stark Classified gene: LDLR as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.83 LDLR Zornitza Stark Gene: ldlr has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.82 LDLR Zornitza Stark gene: LDLR was added
gene: LDLR was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: LDLR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LDLR were set to Hypercholesterolemia, familial, 1, MIM# 143890
Review for gene: LDLR was set to GREEN
Added comment: STRONG actionability in children by ClinGen.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.81 LDLRAP1 Zornitza Stark Marked gene: LDLRAP1 as ready
Genomic screening in children: BabyScreen+ v0.81 LDLRAP1 Zornitza Stark Gene: ldlrap1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.81 LDLRAP1 Zornitza Stark commented on gene: LDLRAP1: DEFINITIVE gene-disease association by ClinGen.

Other FH genes have been assessed as having strong actionability in childhood by ClinGen, included for completeness.
Genomic screening in children: BabyScreen+ v0.81 PCSK9 Zornitza Stark Marked gene: PCSK9 as ready
Genomic screening in children: BabyScreen+ v0.81 PCSK9 Zornitza Stark Gene: pcsk9 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.81 PCSK9 Zornitza Stark reviewed gene: PCSK9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypercholesterolemia, autosomal dominant, 3 MONDO:0011369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.81 APOB Zornitza Stark Marked gene: APOB as ready
Genomic screening in children: BabyScreen+ v0.81 APOB Zornitza Stark Gene: apob has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.81 APOB Zornitza Stark reviewed gene: APOB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypercholesterolemia, autosomal dominant, type B MONDO:0007751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.81 Zornitza Stark Copied gene PCSK9 from panel Familial hypercholesterolaemia
Genomic screening in children: BabyScreen+ v0.81 PCSK9 Zornitza Stark gene: PCSK9 was added
gene: PCSK9 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCSK9 were set to 24404629; 16577715; 15654334
Phenotypes for gene: PCSK9 were set to hypercholesterolemia, autosomal dominant, 3 MONDO:0011369
Mode of pathogenicity for gene: PCSK9 was set to Other
Genomic screening in children: BabyScreen+ v0.80 Zornitza Stark Copied gene LDLRAP1 from panel Familial hypercholesterolaemia
Genomic screening in children: BabyScreen+ v0.80 LDLRAP1 Zornitza Stark gene: LDLRAP1 was added
gene: LDLRAP1 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LDLRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDLRAP1 were set to 4351242
Phenotypes for gene: LDLRAP1 were set to Hypercholesterolemia, familial, 4, MIM# 603813
Genomic screening in children: BabyScreen+ v0.79 Zornitza Stark Copied gene APOB from panel Familial hypercholesterolaemia
Genomic screening in children: BabyScreen+ v0.79 APOB Zornitza Stark gene: APOB was added
gene: APOB was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable tags were added to gene: APOB.
Mode of inheritance for gene: APOB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOB were set to 24404629
Phenotypes for gene: APOB were set to hypercholesterolemia, autosomal dominant, type B MONDO:0007751
Mode of pathogenicity for gene: APOB was set to Other
Genomic screening in children: BabyScreen+ v0.78 ABCC8 Zornitza Stark commented on gene: ABCC8: Multiple gene-disease associations, caution when reporting, only included here for association with MODY.
Genomic screening in children: BabyScreen+ v0.78 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
Genomic screening in children: BabyScreen+ v0.78 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.78 CEL Zornitza Stark Tag for review tag was added to gene: CEL.
Genomic screening in children: BabyScreen+ v0.78 GCK Zornitza Stark Marked gene: GCK as ready
Genomic screening in children: BabyScreen+ v0.78 GCK Zornitza Stark Gene: gck has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.78 GCK Zornitza Stark Phenotypes for gene: GCK were changed from Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851) to MODY, type II, AD (MIM#125851)
Genomic screening in children: BabyScreen+ v0.77 GCK Zornitza Stark Mode of inheritance for gene: GCK was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.76 GCK Zornitza Stark reviewed gene: GCK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MODY, type II, AD (MIM#125851); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.76 HNF1B Zornitza Stark Marked gene: HNF1B as ready
Genomic screening in children: BabyScreen+ v0.76 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.76 INS Zornitza Stark Marked gene: INS as ready
Genomic screening in children: BabyScreen+ v0.76 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.76 INS Zornitza Stark Phenotypes for gene: INS were changed from monogenic diabetes MONDO:0015967; Diabetes mellitus, insulin-dependent, 2, MIM# 125852; Diabetes mellitus, permanent neonatal 4, MIM# 618858; Maturity-onset diabetes of the young, type 10, MIM# 613370 to monogenic diabetes MONDO:0015967
Genomic screening in children: BabyScreen+ v0.75 NEUROD1 Zornitza Stark Marked gene: NEUROD1 as ready
Genomic screening in children: BabyScreen+ v0.75 NEUROD1 Zornitza Stark Gene: neurod1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.75 NEUROD1 Zornitza Stark Phenotypes for gene: NEUROD1 were changed from Maturity Onset Diabetes of the Young; {Diabetes mellitus, noninsulin-dependent}, 125853 to Maturity-onset diabetes of the young 6, MIM#606394
Genomic screening in children: BabyScreen+ v0.74 NEUROD1 Zornitza Stark Mode of inheritance for gene: NEUROD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.73 NEUROD1 Zornitza Stark changed review comment from: Mono-allelic variants in this gene are associated with MODY.

Rare reports of bi-allelic variants, sometimes with permanent neonatal diabetes, RP/retinopathy reported in three unrelated individuals. Functional data to support gene's role in retina.; to: Mono-allelic variants in this gene are associated with MODY.
Genomic screening in children: BabyScreen+ v0.73 NEUROD1 Zornitza Stark edited their review of gene: NEUROD1: Changed phenotypes: Maturity-onset diabetes of the young 6, MIM#606394; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.73 RFX6 Zornitza Stark Marked gene: RFX6 as ready
Genomic screening in children: BabyScreen+ v0.73 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.73 RFX6 Zornitza Stark Phenotypes for gene: RFX6 were changed from maturity-onset diabetes of the young MONDO:0018911 to monogenic diabetes MONDO:0015967
Genomic screening in children: BabyScreen+ v0.72 RFX6 Zornitza Stark Deleted their comment
Genomic screening in children: BabyScreen+ v0.72 RFX6 Zornitza Stark edited their review of gene: RFX6: Changed phenotypes: monogenic diabetes MONDO:0015967; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic screening in children: BabyScreen+ v0.72 Zornitza Stark Copied gene RFX6 from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.72 RFX6 Zornitza Stark gene: RFX6 was added
gene: RFX6 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Expert list,Victorian Clinical Genetics Services
Mode of inheritance for gene: RFX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX6 were set to 20148032; 25048417; 27185633; 29026101; 31001871; 36208030
Phenotypes for gene: RFX6 were set to maturity-onset diabetes of the young MONDO:0018911
Genomic screening in children: BabyScreen+ v0.71 Zornitza Stark Copied gene NEUROD1 from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.71 NEUROD1 Zornitza Stark gene: NEUROD1 was added
gene: NEUROD1 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: NEUROD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NEUROD1 were set to 25477324; 25684977; 22784109; 29521454
Phenotypes for gene: NEUROD1 were set to Maturity Onset Diabetes of the Young; {Diabetes mellitus, noninsulin-dependent}, 125853
Genomic screening in children: BabyScreen+ v0.70 Zornitza Stark Copied gene INS from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.70 INS Zornitza Stark gene: INS was added
gene: INS was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: INS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: INS were set to 18162506; 9884331
Phenotypes for gene: INS were set to monogenic diabetes MONDO:0015967; Diabetes mellitus, insulin-dependent, 2, MIM# 125852; Diabetes mellitus, permanent neonatal 4, MIM# 618858; Maturity-onset diabetes of the young, type 10, MIM# 613370
Genomic screening in children: BabyScreen+ v0.69 Zornitza Stark Copied gene HNF1B from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.69 HNF1B Zornitza Stark gene: HNF1B was added
gene: HNF1B was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
cnv tags were added to gene: HNF1B.
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HNF1B were set to Renal cysts and diabetes syndrome, 137920
Genomic screening in children: BabyScreen+ v0.68 Zornitza Stark Copied gene GCK from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.68 GCK Zornitza Stark gene: GCK was added
gene: GCK was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GCK was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCK were set to 19790256
Phenotypes for gene: GCK were set to Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851)
Genomic screening in children: BabyScreen+ v0.67 Zornitza Stark Copied gene CEL from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.67 CEL Zornitza Stark gene: CEL was added
gene: CEL was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital
technically challenging tags were added to gene: CEL.
Mode of inheritance for gene: CEL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEL were set to 24062244; 21784842; 19760265; 18544793; 17989309; 16369531; 29233499; 27650499
Phenotypes for gene: CEL were set to Maturity-onset diabetes of the young, type VIII, 609812
Genomic screening in children: BabyScreen+ v0.66 Zornitza Stark Copied gene ABCC8 from panel Maturity-onset Diabetes of the Young
Genomic screening in children: BabyScreen+ v0.66 ABCC8 Zornitza Stark gene: ABCC8 was added
gene: ABCC8 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ABCC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC8 were set to 21989597; 34014594
Phenotypes for gene: ABCC8 were set to Maturity-onset diabetes of the young, type 12, MIM# 621196
Genomic screening in children: BabyScreen+ v0.65 SCN5A Zornitza Stark Marked gene: SCN5A as ready
Genomic screening in children: BabyScreen+ v0.65 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.65 SCN5A Zornitza Stark Classified gene: SCN5A as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.65 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.64 SCN5A Zornitza Stark changed review comment from: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.

Reviewed with paediatric cardiologist: generally later age of onset, does not fulfil criteria for gNBS.; to: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.
Genomic screening in children: BabyScreen+ v0.64 SCN5A Zornitza Stark edited their review of gene: SCN5A: Changed rating: GREEN
Genomic screening in children: BabyScreen+ v0.64 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
Genomic screening in children: BabyScreen+ v0.64 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.64 PRKG1 Zornitza Stark Classified gene: PRKG1 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.64 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.63 PRKG1 Zornitza Stark edited their review of gene: PRKG1: Changed rating: GREEN
Genomic screening in children: BabyScreen+ v0.63 PKP2 Zornitza Stark Marked gene: PKP2 as ready
Genomic screening in children: BabyScreen+ v0.63 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.63 PKP2 Zornitza Stark Classified gene: PKP2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.63 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.62 PKP2 Zornitza Stark edited their review of gene: PKP2: Changed rating: GREEN
Genomic screening in children: BabyScreen+ v0.62 STK11 Zornitza Stark Marked gene: STK11 as ready
Genomic screening in children: BabyScreen+ v0.62 STK11 Zornitza Stark Gene: stk11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.62 Zornitza Stark Copied gene SCN5A from panel Genomic newborn screening: BabyScreen+
Genomic screening in children: BabyScreen+ v0.62 SCN5A Zornitza Stark gene: SCN5A was added
gene: SCN5A was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Amber,BabySeq Category B gene,BeginNGS
cardiac, treatable tags were added to gene: SCN5A.
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCN5A were set to Long QT syndrome 3 (MIM#603830); Brugada syndrome 1, MIM# 601144
Genomic screening in children: BabyScreen+ v0.61 Zornitza Stark Copied gene PRKG1 from panel Genomic newborn screening: BabyScreen+
Genomic screening in children: BabyScreen+ v0.61 PRKG1 Zornitza Stark gene: PRKG1 was added
gene: PRKG1 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Amber,ClinGen
cardiac, treatable tags were added to gene: PRKG1.
Mode of inheritance for gene: PRKG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKG1 were set to Aortic aneurysm, familial thoracic 8, MIM#615436
Penetrance for gene: PRKG1 were set to Incomplete
Genomic screening in children: BabyScreen+ v0.60 Zornitza Stark Copied gene PKP2 from panel Genomic newborn screening: BabyScreen+
Genomic screening in children: BabyScreen+ v0.60 PKP2 Zornitza Stark gene: PKP2 was added
gene: PKP2 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review Amber,BabySeq Category B gene
for review, cardiac, treatable tags were added to gene: PKP2.
Mode of inheritance for gene: PKP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PKP2 were set to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
Genomic screening in children: BabyScreen+ v0.59 SMARCAL1 Lilian Rudd gene: SMARCAL1 was added
gene: SMARCAL1 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCAL1 were set to PMID: 20301550
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia MIM#242900
Review for gene: SMARCAL1 was set to GREEN
Added comment: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: haematopoietic stem cells transplantation, renal transplant described.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.58 SPTLC1 Lilian Rudd gene: SPTLC1 was added
gene: SPTLC1 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: SPTLC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTLC1 were set to PMID: 34059824
Phenotypes for gene: SPTLC1 were set to Amyotrophic lateral sclerosis 27, juvenile MIM#620285
Review for gene: SPTLC1 was set to GREEN
Added comment: Specific variants (exon 2) cause the childhood onset.
Treatment serine
Non-genetic confirmatory test: Sphingolipid levels
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.57 STK11 Lilian Rudd Classified gene: STK11 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.57 STK11 Lilian Rudd Gene: stk11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.56 STK11 Lilian Rudd gene: STK11 was added
gene: STK11 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STK11 were set to Peutz-Jeghers syndrome MIM#175200
Review for gene: STK11 was set to GREEN
Added comment: Established gene-disease association.

Cancer predisposition. Minor manifestations in early childhood, but ~30% of pre-teens require surgical intervention to alleviate polyp related symptoms. Adult cancer risk managed largely surgically. Surveillance (baseline endoscopy) recommended from 8 years old.

Treatment: Surgical intervention and symptoms management

Non-genetic confirmatory test: N/A
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.55 TECRL Lilian Rudd Marked gene: TECRL as ready
Genomic screening in children: BabyScreen+ v0.55 TECRL Lilian Rudd Gene: tecrl has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.55 TECRL Lilian Rudd Classified gene: TECRL as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.55 TECRL Lilian Rudd Gene: tecrl has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.54 TECRL Lilian Rudd gene: TECRL was added
gene: TECRL was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen. Not on ACMG additional findings list.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.53 TNFRSF11B Lilian Rudd Marked gene: TNFRSF11B as ready
Genomic screening in children: BabyScreen+ v0.53 TNFRSF11B Lilian Rudd Gene: tnfrsf11b has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.53 TNFRSF11B Lilian Rudd Classified gene: TNFRSF11B as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.53 TNFRSF11B Lilian Rudd Gene: tnfrsf11b has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.52 TNFRSF11B Lilian Rudd gene: TNFRSF11B was added
gene: TNFRSF11B was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: TNFRSF11B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF11B were set to PMID: 29080812; 25108083; 34166796
Phenotypes for gene: TNFRSF11B were set to Paget disease of bone 5, juvenile-onset MIM#239000
Review for gene: TNFRSF11B was set to GREEN
Added comment: Strong gene disease association
Causes generalised rapid bone turnover due to osteoprotogerin (OPG) deficiency
Short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness - also vascular risk of calcification and aneurysms
Variable age of onset - mostly early childhood but with bi-allelic missense can be later onset
Treatment evidence is from case reports or case series only.
Bisphosphanates - available and if started early alter disease course
recombinant OPG - available in clinical trials for other indications only
denosumab - monoclonal antibody - tried in a handful of patients, not sufficient evidence in children.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.51 TRDN Lilian Rudd Classified gene: TRDN as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.51 TRDN Lilian Rudd Gene: trdn has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.50 TRDN Lilian Rudd gene: TRDN was added
gene: TRDN was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRDN were set to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441
Review for gene: TRDN was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.49 ZBTB24 Lilian Rudd Marked gene: ZBTB24 as ready
Genomic screening in children: BabyScreen+ v0.49 ZBTB24 Lilian Rudd Added comment: Comment when marking as ready: Red - on ID list for opt in .
Genomic screening in children: BabyScreen+ v0.49 ZBTB24 Lilian Rudd Gene: zbtb24 has been classified as Red List (Low Evidence).
Genomic screening in children: BabyScreen+ v0.49 TTN Lilian Rudd gene: TTN was added
gene: TTN was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: TTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TTN were set to PMID: 22335739; 40796136
Phenotypes for gene: TTN were set to Cardiomyopathy, dilated, 1G MIM#604145
Review for gene: TTN was set to AMBER
Added comment: Definitive gene disease association for DCM
On ACMG additional findings list for truncating variants only
Age of onset can be childhood but this might be better for adolescent screening due to higher penetrance with age?
I think probably red?
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.48 VWF Lilian Rudd gene: VWF was added
gene: VWF was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: VWF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VWF were set to von Willebrand disease, type 3 MIM#277480
Review for gene: VWF was set to AMBER
Added comment: Recessive more severe form suitable for screening as treatable with desmopressin/FVIII/VWF particularly around surgery.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.47 ZBTB24 Lilian Rudd gene: ZBTB24 was added
gene: ZBTB24 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to PMID: 28128455, 21906047, 21596365, 23486536
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069
Review for gene: ZBTB24 was set to AMBER
Added comment: Infant onset
Agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds.
Treat immunoglobulin and bone marrow transplant however, this only treats the immune deficiency.
?For childhood screening or just for ID opt in.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.46 MYH11 Zornitza Stark Tag cardiac tag was added to gene: MYH11.
Tag treatable tag was added to gene: MYH11.
Genomic screening in children: BabyScreen+ v0.46 MEN1 Zornitza Stark Tag cancer tag was added to gene: MEN1.
Tag treatable tag was added to gene: MEN1.
Genomic screening in children: BabyScreen+ v0.46 LOX Zornitza Stark Tag cardiac tag was added to gene: LOX.
Tag treatable tag was added to gene: LOX.
Genomic screening in children: BabyScreen+ v0.46 LAMP2 Zornitza Stark Tag cardiac tag was added to gene: LAMP2.
Tag treatable tag was added to gene: LAMP2.
Genomic screening in children: BabyScreen+ v0.46 JUP Zornitza Stark Tag cardiac tag was added to gene: JUP.
Tag treatable tag was added to gene: JUP.
Genomic screening in children: BabyScreen+ v0.46 HNF1A Zornitza Stark Tag treatable tag was added to gene: HNF1A.
Tag endocrine tag was added to gene: HNF1A.
Genomic screening in children: BabyScreen+ v0.46 DSP Zornitza Stark Tag cardiac tag was added to gene: DSP.
Tag treatable tag was added to gene: DSP.
Genomic screening in children: BabyScreen+ v0.46 DSG2 Zornitza Stark Tag cardiac tag was added to gene: DSG2.
Tag treatable tag was added to gene: DSG2.
Genomic screening in children: BabyScreen+ v0.46 DSC2 Zornitza Stark Tag cardiac tag was added to gene: DSC2.
Tag treatable tag was added to gene: DSC2.
Genomic screening in children: BabyScreen+ v0.46 DMD Zornitza Stark Tag clinical trial tag was added to gene: DMD.
Tag neurological tag was added to gene: DMD.
Genomic screening in children: BabyScreen+ v0.46 COL3A1 Zornitza Stark Tag cardiac tag was added to gene: COL3A1.
Tag treatable tag was added to gene: COL3A1.
Genomic screening in children: BabyScreen+ v0.46 CASQ2 Zornitza Stark Tag cardiac tag was added to gene: CASQ2.
Tag treatable tag was added to gene: CASQ2.
Genomic screening in children: BabyScreen+ v0.46 CALM2 Zornitza Stark Tag cardiac tag was added to gene: CALM2.
Tag treatable tag was added to gene: CALM2.
Genomic screening in children: BabyScreen+ v0.46 CALM1 Zornitza Stark Tag cardiac tag was added to gene: CALM1.
Tag treatable tag was added to gene: CALM1.
Genomic screening in children: BabyScreen+ v0.46 MYH11 Zornitza Stark Marked gene: MYH11 as ready
Genomic screening in children: BabyScreen+ v0.46 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.46 MYH11 Zornitza Stark Classified gene: MYH11 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.46 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.45 MYH11 Zornitza Stark gene: MYH11 was added
gene: MYH11 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: MYH11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYH11 were set to Aortic aneurysm, familial thoracic 4, MIM#160745
Review for gene: MYH11 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.
Sources: Expert list
Genomic screening in children: BabyScreen+ v0.44 MEN1 Zornitza Stark Marked gene: MEN1 as ready
Genomic screening in children: BabyScreen+ v0.44 MEN1 Zornitza Stark Gene: men1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.44 MEN1 Zornitza Stark Classified gene: MEN1 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.44 MEN1 Zornitza Stark Gene: men1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.43 MEN1 Zornitza Stark gene: MEN1 was added
gene: MEN1 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MEN1 were set to Multiple endocrine neoplasia 1, MIM#131100
Review for gene: MEN1 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

Parathyroid tumors, which cause PHPT, are the most common feature and the first clinical manifestation in 90% of individuals with MEN1 with onset typically between ages 20 and 25 years. Almost all (95-100%) individuals with MEN1 can expect to have PHPT by age 50 years. However, MEN1 affects all age groups, with a reported age range of 5 to 81 years; 17% of MEN1 tumors are diagnosed under age 21. Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by age 50. The cause of death in 50-70% of cases is due to a malignant tumor process or sequelae of the disease, with malignancies accounting for 30% of all deaths.

Surveillance generally recommended 5yo onwards.
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.42 LOX Zornitza Stark Marked gene: LOX as ready
Genomic screening in children: BabyScreen+ v0.42 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.42 LOX Zornitza Stark Classified gene: LOX as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.42 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.41 LOX Zornitza Stark gene: LOX was added
gene: LOX was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, MIM#617168
Review for gene: LOX was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.40 LAMP2 Zornitza Stark changed review comment from: X-linked dominant genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neurocognitive deficits
Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias. The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death. Males are typically more severely affected than females.

Early onset cardiomyoapthy and neurodevelopmental phenotype - reproductive utility to prevent multiple affected pregnancies. High-penetrance cardiomyopathy with high risk of arrhythmia and or transplant. Neurodevelopmental issues allow preparation and early childhood intervention.
- Ages of onset in Cohort studies and personal experience M 0.25–45 F2–58
- The family known to RCH/MMC is neonatal onset cardiomyopathy, symptomatic, potentially we should publish more formally, was presented at HGSA

International natural history study ongoing.
Expect therapy in next few years. Trials ongoing in Europe and US with therapy for CM and improvement in ND outcomes.
Rocket Pharmaceuticals Adeno-associated- vector-501 (RP-A501) (AAV9.LAMP2B), an investigational gene therapy product for DD and the first potential gene therapy for monogenic heart failure.
Sources: Expert Review; to: X-linked dominant genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neurocognitive deficits
Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias. The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death. Males are typically more severely affected than females.

Early onset cardiomyoapthy and neurodevelopmental phenotype - reproductive utility to prevent multiple affected pregnancies. High-penetrance cardiomyopathy with high risk of arrhythmia and or transplant. Neurodevelopmental issues allow preparation and early childhood intervention.
- Ages of onset in Cohort studies and personal experience M 0.25–45 F2–58
- The family known to RCH/MMC is neonatal onset cardiomyopathy, symptomatic, potentially we should publish more formally, was presented at HGSA

International natural history study ongoing.
Expect therapy in next few years. Trials ongoing in Europe and US with therapy for CM and improvement in ND outcomes.
Rocket Pharmaceuticals Adeno-associated- vector-501 (RP-A501) (AAV9.LAMP2B), an investigational gene therapy product for DD and the first potential gene therapy for monogenic heart failure.

MODERATE actionability in paediatric patients by ClinGen.
Genomic screening in children: BabyScreen+ v0.40 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Genomic screening in children: BabyScreen+ v0.40 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.40 LAMP2 Zornitza Stark Classified gene: LAMP2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.40 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.39 LAMP2 Zornitza Stark gene: LAMP2 was added
gene: LAMP2 was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: LAMP2 were set to Danon disease, MIM# 300257
Review for gene: LAMP2 was set to GREEN
Added comment: X-linked dominant genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neurocognitive deficits
Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias. The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death. Males are typically more severely affected than females.

Early onset cardiomyoapthy and neurodevelopmental phenotype - reproductive utility to prevent multiple affected pregnancies. High-penetrance cardiomyopathy with high risk of arrhythmia and or transplant. Neurodevelopmental issues allow preparation and early childhood intervention.
- Ages of onset in Cohort studies and personal experience M 0.25–45 F2–58
- The family known to RCH/MMC is neonatal onset cardiomyopathy, symptomatic, potentially we should publish more formally, was presented at HGSA

International natural history study ongoing.
Expect therapy in next few years. Trials ongoing in Europe and US with therapy for CM and improvement in ND outcomes.
Rocket Pharmaceuticals Adeno-associated- vector-501 (RP-A501) (AAV9.LAMP2B), an investigational gene therapy product for DD and the first potential gene therapy for monogenic heart failure.
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.38 DMD Zornitza Stark Marked gene: DMD as ready
Genomic screening in children: BabyScreen+ v0.38 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.38 DMD Zornitza Stark Classified gene: DMD as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.38 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.37 DMD Zornitza Stark gene: DMD was added
gene: DMD was added to Genomic screening in children: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: DMD were set to Duchenne muscular dystrophy MIM#310200
Review for gene: DMD was set to GREEN
Added comment: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only.

Onset in early childhood.

Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping.

Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels.

Discussed with Neurology: include.
Sources: Expert Review
Genomic screening in children: BabyScreen+ v0.36 JUP Zornitza Stark Marked gene: JUP as ready
Genomic screening in children: BabyScreen+ v0.36 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.36 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
Genomic screening in children: BabyScreen+ v0.35 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.34 JUP Zornitza Stark Classified gene: JUP as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.34 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.33 JUP Zornitza Stark edited their review of gene: JUP: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.33 HNF4A Zornitza Stark Marked gene: HNF4A as ready
Genomic screening in children: BabyScreen+ v0.33 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.33 HNF4A Zornitza Stark Phenotypes for gene: HNF4A were changed from to MODY, type I, OMIM # 125850
Genomic screening in children: BabyScreen+ v0.32 HNF4A Zornitza Stark Classified gene: HNF4A as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.32 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.31 HNF4A Zornitza Stark edited their review of gene: HNF4A: Added comment: At the milder end of the spectrum, variants in this gene are associated with MODY.

Treatment of hyperinsulinism: diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus.; Changed phenotypes: MODY, type I, OMIM # 125850
Genomic screening in children: BabyScreen+ v0.31 HNF1A Zornitza Stark Marked gene: HNF1A as ready
Genomic screening in children: BabyScreen+ v0.31 HNF1A Zornitza Stark Gene: hnf1a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.31 HNF1A Zornitza Stark Phenotypes for gene: HNF1A were changed from to MODY, type III , MIM#600496
Genomic screening in children: BabyScreen+ v0.30 HNF1A Zornitza Stark edited their review of gene: HNF1A: Added comment: Established gene-disease association.

Onset is generally under 25 years.

Treatment: diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus; Changed phenotypes: MODY, type III , MIM#600496
Genomic screening in children: BabyScreen+ v0.30 HNF1A Zornitza Stark Classified gene: HNF1A as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.30 HNF1A Zornitza Stark Gene: hnf1a has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.29 HGD Zornitza Stark Marked gene: HGD as ready
Genomic screening in children: BabyScreen+ v0.29 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.29 HGD Zornitza Stark Phenotypes for gene: HGD were changed from to Alkaptonuria MIM#203500
Genomic screening in children: BabyScreen+ v0.28 HGD Zornitza Stark Classified gene: HGD as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.28 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.27 HGD Zornitza Stark Tag treatable tag was added to gene: HGD.
Tag metabolic tag was added to gene: HGD.
Genomic screening in children: BabyScreen+ v0.27 HGD Zornitza Stark edited their review of gene: HGD: Added comment: Well established gene-disease association.

Progressive metabolic disorder; however, symptoms generally appear in adulthood.

Treatable: Nitisinone, diet

Low dose nitisinone greatly reduces homogentisic acid levels and if started early will probably prevent the clinical abnormalities from developing, hence potential benefit from screening in childhood. Dark urine also tends to manifest in childhood.; Changed phenotypes: Alkaptonuria MIM#203500
Genomic screening in children: BabyScreen+ v0.27 DSP Zornitza Stark Marked gene: DSP as ready
Genomic screening in children: BabyScreen+ v0.27 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.27 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
Genomic screening in children: BabyScreen+ v0.26 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.25 DSP Zornitza Stark Classified gene: DSP as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.25 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.24 DSP Zornitza Stark edited their review of gene: DSP: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.24 DSP Zornitza Stark edited their review of gene: DSP: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
Genomic screening in children: BabyScreen+ v0.24 DSG2 Zornitza Stark Marked gene: DSG2 as ready
Genomic screening in children: BabyScreen+ v0.24 DSG2 Zornitza Stark Gene: dsg2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.24 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
Genomic screening in children: BabyScreen+ v0.23 DSG2 Zornitza Stark Classified gene: DSG2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.23 DSG2 Zornitza Stark Gene: dsg2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.22 DSG2 Zornitza Stark edited their review of gene: DSG2: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
Genomic screening in children: BabyScreen+ v0.22 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Genomic screening in children: BabyScreen+ v0.22 DSC2 Zornitza Stark Gene: dsc2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.22 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
Genomic screening in children: BabyScreen+ v0.21 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.20 DSC2 Zornitza Stark Classified gene: DSC2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.20 DSC2 Zornitza Stark Gene: dsc2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.19 DSC2 Zornitza Stark edited their review of gene: DSC2: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; Changed phenotypes: Arrhythmogenic right ventricular dysplasia 11, MIM# 610476, Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic screening in children: BabyScreen+ v0.19 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Genomic screening in children: BabyScreen+ v0.19 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.19 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Ehlers-Danlos syndrome, vascular type, MIM# 130050
Genomic screening in children: BabyScreen+ v0.18 COL3A1 Zornitza Stark Classified gene: COL3A1 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.18 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.17 COL3A1 Zornitza Stark edited their review of gene: COL3A1: Added comment: Well established gene-disease association.

Assessed as 'moderate actionability' in paediatric patients by ClinGen.

Approximately half of children tested for vEDS in the absence of a positive family history present with a major complication at an average age of 11 years. The majority (60%) of individuals diagnosed before age 18 are identified because of a positive family history, though 15% of children have experienced a major complication before the time of testing, and of those tested in the absence of family history, 54% had experienced a major complication.

Death in the first two decades of life most commonly results from arterial rupture; death before age 20 is more commonly reported in males (3:1). Vascular rupture or dissection and gastrointestinal perforation or organ rupture are the presenting signs in 70% of adults with a COL3A1 pathogenic variant, and may present as sudden death, stroke and neurologic sequelae, acute abdomen/retroperitoneal bleeding, uterine rupture at delivery, and/or shock, with an average age of 31 for first major arterial or gastrointestinal complication. Bowel rupture is very rarely (3%) lethal. Hemoptysis can be severe and recurrent, even life threatening. Carotid cavernous sinus fistulas typically present with sudden-onset ocular symptoms and almost always require rapid intervention to save vision. It affects about 10% of individuals with vEDS with a preponderance among females. Vascular fragility is dominant in the third and fourth decade.

Imaging of the entire arterial tree is recommended.

Lack of consensus re aortic repair: Guidelines differ on recommendation for prophylactic aortic repair in the case of asymptomatic patients with aortic aneurysm. Some guidelines recommend patients undergo elective operation at diameters of 4.0-6.0 cm depending on location of aortic aneurysm and pregnancy anticipation status. Other guidelines take a more conservative approach, stating that due to the high risk of complications as a result of hemorrhagic tendency, tissue fragility, and poor wound healing in vEDS as well as the lack of specific data in vEDS patients, it is not possible to set threshold for surgical intervention in patients with EDS Type IV and thoracic aortic aneurysm. These guidelines state that decisions to surgically intervene should instead be based on a case-by-case basis and guided by multidisciplinary discussion.

On ACMG SF list.; Changed phenotypes: Ehlers-Danlos syndrome, vascular type, MIM# 130050
Genomic screening in children: BabyScreen+ v0.17 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
Genomic screening in children: BabyScreen+ v0.17 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.17 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Genomic screening in children: BabyScreen+ v0.16 CASQ2 Zornitza Stark Classified gene: CASQ2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.16 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.15 CASQ2 Zornitza Stark edited their review of gene: CASQ2: Added comment: ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Genomic screening in children: BabyScreen+ v0.15 CALM2 Zornitza Stark Marked gene: CALM2 as ready
Genomic screening in children: BabyScreen+ v0.15 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.15 CALM2 Zornitza Stark Phenotypes for gene: CALM2 were changed from to Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Genomic screening in children: BabyScreen+ v0.14 CALM2 Zornitza Stark Classified gene: CALM2 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.14 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.13 CALM2 Zornitza Stark edited their review of gene: CALM2: Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.; Changed phenotypes: Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Genomic screening in children: BabyScreen+ v0.13 CALM1 Zornitza Stark Marked gene: CALM1 as ready
Genomic screening in children: BabyScreen+ v0.13 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.13 CALM1 Zornitza Stark Phenotypes for gene: CALM1 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916
Genomic screening in children: BabyScreen+ v0.12 CALM1 Zornitza Stark Classified gene: CALM1 as Green List (high evidence)
Genomic screening in children: BabyScreen+ v0.12 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Genomic screening in children: BabyScreen+ v0.11 CALM1 Zornitza Stark edited their review of gene: CALM1: Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916
Genomic screening in children: BabyScreen+ v0.11 JUP Zornitza Stark gene: JUP was added
gene: JUP was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: JUP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: JUP was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.10 HNF4A Zornitza Stark gene: HNF4A was added
gene: HNF4A was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: HNF4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: HNF4A was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.9 HNF1A Zornitza Stark gene: HNF1A was added
gene: HNF1A was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: HNF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: HNF1A was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.8 HGD Zornitza Stark gene: HGD was added
gene: HGD was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: HGD was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: HGD was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.7 DSP Zornitza Stark gene: DSP was added
gene: DSP was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: DSP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: DSP was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.6 DSG2 Zornitza Stark gene: DSG2 was added
gene: DSG2 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: DSG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: DSG2 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.5 DSC2 Zornitza Stark gene: DSC2 was added
gene: DSC2 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: DSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: DSC2 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.4 COL3A1 Zornitza Stark gene: COL3A1 was added
gene: COL3A1 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: COL3A1 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.3 CASQ2 Zornitza Stark gene: CASQ2 was added
gene: CASQ2 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: CASQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: CASQ2 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.2 CALM2 Zornitza Stark gene: CALM2 was added
gene: CALM2 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: CALM2 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.1 CALM1 Zornitza Stark gene: CALM1 was added
gene: CALM1 was added to Genomic screening in children: BabyScreen+. Sources: Expert list
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: CALM1 was set to GREEN
Added comment: Sources: Expert list
Genomic screening in children: BabyScreen+ v0.0 Zornitza Stark Added Panel Genomic screening in children: BabyScreen+
Set panel types to: Victorian Clinical Genetics Services