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| Congenital hyperinsulinism v2.33 | CACNA1C | Eleanor Williams Phenotypes for gene: CACNA1C were changed from non-syndromic congeital hyperinsulinism; Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979 to non-syndromic congeital hyperinsulinism; Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979; CACNA1C-related disorder | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.32 | CACNA1C |
Arina Puzriakova Tag Q3_22_rating was removed from gene: CACNA1C. Tag Q3_22_MOI was removed from gene: CACNA1C. Tag Q3_22_NHS_review was removed from gene: CACNA1C. |
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| Congenital hyperinsulinism v2.32 | CACNA1C | Arina Puzriakova reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.31 | CACNA1C |
Arina Puzriakova Source Expert Review Green was added to CACNA1C. Source NHS GMS was added to CACNA1C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Congenital hyperinsulinism v2.21 | CACNA1C | Sarah Leigh Tag Q3_22_MOI tag was added to gene: CACNA1C. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.21 | CACNA1C |
Sarah Leigh Tag Q3_22_rating tag was added to gene: CACNA1C. Tag Q3_22_NHS_review tag was added to gene: CACNA1C. |
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| Congenital hyperinsulinism v2.21 | CACNA1C | Sarah Leigh Classified gene: CACNA1C as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.21 | CACNA1C | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.21 | CACNA1C | Sarah Leigh Gene: cacna1c has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.20 | CACNA1C |
Sarah Leigh edited their review of gene: CACNA1C: Added comment: Associated with in OMIM and as definitive Gen2Phen gene for Timothy syndrome (OMIM:601005). At least two CACNA1C variants have been reported in numerous cases of Timothy syndrome. PMID: 35897673 reports novel heterozygous CACNA1C variant in a patient with congenital hyperinsulinism (CHI), which appears to have gain-of-function and loss-of-function effects at the electrophysiological level, explaining the hyperinsulinism and resulting hypoglycemia in the patient reported. It appeared that c.1679T>C, p.L566P (NM_000719.6) reported in this patient has a minor effects on the cardiac action potential in an in silico model, in contrast to c.1216G>T, p.G406R (NM_000719.6) which is associated with the Long QT in Timothy syndrome (OMIM:601005). Therefore the authors conclude that this represents a novel congeital non-syndromic hyperinsulinism. Hypoglycemia is also seen in Timothy syndrome patients with c.1216G>T, p.G406R (Table S3, PMID: 35897673), it would therefore be appropriate to screen other patients with hyperinsulinism / hypoglycemia for CACNA1C variants.; Changed rating: GREEN |
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| Congenital hyperinsulinism v2.20 | CACNA1C | Sarah Leigh Phenotypes for gene: CACNA1C were changed from non-syndromic congeital hyperinsulinism to non-syndromic congeital hyperinsulinism; Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.19 | CACNA1C | Sarah Leigh Added comment: Comment on mode of pathogenicity: In vitro studies show that c.1679T>C, p.Leu566Pro (NM_000719.6) appears to have loss-of-function effects by altering current amplitudes in mutant channels and a gain-of-function effect by slowing the voltage-dependent inactivation (PMID: 35897673). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.19 | CACNA1C | Sarah Leigh Mode of pathogenicity for gene: CACNA1C was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.18 | CACNA1C | Sarah Leigh Phenotypes for gene: CACNA1C were changed from to non-syndromic congeital hyperinsulinism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.14 | CACNA1C | Sarah Leigh Publications for gene: CACNA1C were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.13 | CACNA1C | Sarah Leigh Mode of inheritance for gene: CACNA1C was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.12 | CACNA1C | Eleanor Williams reviewed gene: CACNA1C: Rating: ; Mode of pathogenicity: ; Publications: 35897673; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hyperinsulinism v2.11 | CACNA1C |
Eleanor Williams gene: CACNA1C was added gene: CACNA1C was added to Congenital hyperinsulinism. Sources: Expert review Mode of inheritance for gene: CACNA1C was set to |
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