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| Renal Macrocystic Disease v0.60 | SEC63 | Chirag Patel Classified gene: SEC63 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.60 | SEC63 | Chirag Patel Gene: sec63 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.59 | SEC63 |
Chirag Patel edited their review of gene: SEC63: Added comment: CLINGEN assessed as DEFINITIVE (2020) SEC63 was FIRST reported in relation to autosomal dominant polycystic liver disease (ADPLD) in 2004 (Davila et al., PMID 15133510). ADPLD due to SEC63 mutations (ADPLD-SEC63) is diagnosed in adults with a family history of liver cysts, under age 40 with any number of liver cysts and individuals over the age of 40 with four or more liver cysts. Women are associated with more severe course of disease, and kidney cysts are present in approximately 28-35% of cases, but in these cases the kidney disease is mild with no association with progression to end stage renal disease (PMID 20408995). At least twenty unique variants (e.g. nonsense, frameshift, splice site, missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, population data and experimental data. Summary of Case Level Data: 12 POINTS. Variants in this gene have been reported in at least 19 probands and in at least four publications (PMID 15133510, PMID 16835903, PMID 20095989, PMID 28375157). Variants in this gene segregated with disease in at least 24 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is heterozygous loss of function (PMID 15133510, PMID 20095989), with experimental evidence suggesting endoplasmic reticulum stress with induction of the unfolded protein response (UPR) and association with aberrant polycystin 1 (PC1) post-translational modifications leading to cystogenesis (PMID 22864019, PMID 25844898). This gene-disease association is supported by expression studies in cell models, zebrafish models, and mouse models (PMID 21685914, PMID 22864019, PMID 25844898). In summary, SEC63 is definitively associated with AUTOSOMAL DOMINANT POLYCYSTIC LIVER DISEASE. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.; Changed rating: GREEN |
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| Renal Macrocystic Disease v0.31 | SEC63 | Zornitza Stark edited their review of gene: SEC63: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.13 | SEC63 | Chirag Patel changed review comment from: Very few renal cysts seen in patients. If this PLD gene is in the panel, then we should have all the PLD genes, where very occasional renal cysts can be seen.; to: Renal cysts not a key or common feature seen in these patients. If this PLD gene is in the panel, then we should have all the PLD genes, where very occasional renal cysts can be seen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.13 | SEC63 | Zornitza Stark Classified gene: SEC63 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.13 | SEC63 | Zornitza Stark Added comment: Comment on list classification: Discussed with Chirag Patel: we should have a consistent approach to all liver cystic disease genes. Renal cysts are not a key feature, therefore Red for this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.13 | SEC63 | Zornitza Stark Gene: sec63 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.12 | SEC63 | Chirag Patel reviewed gene: SEC63: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic liver disease 2, OMIM #617004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.12 | SEC63 | Zornitza Stark Marked gene: SEC63 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.12 | SEC63 | Zornitza Stark Gene: sec63 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.12 | SEC63 | Zornitza Stark Classified gene: SEC63 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.12 | SEC63 | Zornitza Stark Gene: sec63 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.11 | SEC63 |
Zornitza Stark gene: SEC63 was added gene: SEC63 was added to Renal macrocystic disease_KidGen_VCGS. Sources: Expert list Mode of inheritance for gene: SEC63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEC63 were set to 15133510 Phenotypes for gene: SEC63 were set to Polycystic liver disease 2, MIM#617004 Review for gene: SEC63 was set to GREEN Added comment: Renal cysts reported in some individuals; no significant renal impairment. Sources: Expert list |
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