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| Mackenzie's Mission_Reproductive Carrier Screening v0.58 | ABCA4 | Seb Lunke Phenotypes for gene: ABCA4 were changed from Cone-rod dystrophy 3, 604116 (3) to Stargardt disease 1 MIM#248200; Retinal dystrophy, early-onset severe MIM#248200; Cone-rod dystrophy 3 MIM#604116 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mackenzie's Mission_Reproductive Carrier Screening v0.54 | ABCA4 | Sarah Righetti reviewed gene: ABCA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Stargardt disease 1 MIM#248200, Retinal dystrophy, early-onset severe MIM#248200, Cone-rod dystrophy 3 MIM#604116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mackenzie's Mission_Reproductive Carrier Screening v0.31 | KCNE1 |
Seb Lunke changed review comment from: Comment by Ivan Macciocca: as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group: Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS. Comment by Zornitza Stark: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited. Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463); to: Comment by Ivan Macciocca: as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group: Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS. Comment by Zornitza Stark: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited. Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463) Association with Long-QT is questionable. Remains GREEN for Deafness, but on balance does not currently meet inclusion criteria for Mackenzie's Mission |
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| Mackenzie's Mission_Reproductive Carrier Screening v0.0 | STAR |
Zornitza Stark gene: STAR was added gene: STAR was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STAR were set to Lipoid adrenal hyperplasia, 201710 (3) |
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