| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Hypertrophic cardiomyopathy v4.7 | ALPK3 | Dmitrijs Rots commented on gene: ALPK3: As described by Luis Lopes, should be BOTH monoallelic and biallelic on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v3.3 | ALPK3 | Arina Puzriakova Tag Q2_22_rating was removed from gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v3.3 | ALPK3 | Arina Puzriakova reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v3.2 | ALPK3 |
Arina Puzriakova Source Expert Review Green was added to ALPK3. Source NHS GMS was added to ALPK3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Hypertrophic cardiomyopathy v2.39 | ALPK3 | Ivone Leong Tag Q2_22_rating tag was added to gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.39 | ALPK3 | Ivone Leong Added comment: Comment on publications: New publications added. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.39 | ALPK3 | Ivone Leong Publications for gene: ALPK3 were set to 26846950; 27106955; 32480058; 28630369; 30046096; 31074094; 21441111 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.38 | ALPK3 | Luis Lopes reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34263907, 35583889; Phenotypes: Hypertrophic Cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.33 | ALPK3 | Ivone Leong Tag Q3_21_MOI was removed from gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.33 | ALPK3 |
Ivone Leong Tag Q3_21_NHS_review was removed from gene: ALPK3. Tag Q3_21_expert_review was removed from gene: ALPK3. |
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| Hypertrophic cardiomyopathy v2.33 | ALPK3 | Ivone Leong Tag for-review was removed from gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.33 | ALPK3 | Ivone Leong commented on gene: ALPK3: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.27 | ALPK3 | Ivone Leong Tag Q3_21_NHS_review tag was added to gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.27 | ALPK3 | Ivone Leong Phenotypes for gene: ALPK3 were changed from Cardiomyopathy, familial hypertrophic 27, 618052 to Cardiomyopathy, familial hypertrophic 27, OMIM:618052 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.26 | ALPK3 | Ivone Leong Tag Q3_21_expert_review tag was added to gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.26 | ALPK3 | Ivone Leong Tag Q3_21_MOI tag was added to gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.26 | ALPK3 | Oliver Watkinson reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32480058; Phenotypes: Hypertrophic Cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.22 | ALPK3 | Dmitrijs Rots reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32480058; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.14 | ALPK3 |
Ivone Leong Added comment: Comment on mode of inheritance: MOI has been changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BIALLELIC, autosomal or pseudoautosomal". All the published cases of affected individuals have homozygous variants in this gene. However, family members who are heterozygous for the ALPK3 variants either show no cardiac phenotype or have later-onset cardiomyopathy or an atypical distribution of hypertrophy (PMID: 26846950, 30046096, 2710685, 32480058). PMID: 32480058 found that some individuals with heterozygous variants in ALPK3 are diagnosed with HCM when they are adults. The paper suggests that LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. More evidence is needed for heterozygous variants in ALPK3 contributing to disease, so therefore the change of MOI. The inclusion of heterozygous variants of ALPK3 will be reviewed at the next panel review. |
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| Hypertrophic cardiomyopathy v2.14 | ALPK3 | Ivone Leong Mode of inheritance for gene: ALPK3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.11 | ALPK3 | Ivone Leong Tag for-review tag was added to gene: ALPK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.11 | ALPK3 | Ivone Leong Classified gene: ALPK3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.11 | ALPK3 | Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to support a gene-disease assocation for it to be Green. This gene will be promoted to Green at the next panel review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.11 | ALPK3 | Ivone Leong Gene: alpk3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.10 | ALPK3 |
Ivone Leong Added comment: Comment on publications: PMID: 28630369. An additional case. Non-consanguineous family of Turkish decent. Fetus was homozgyous for variant and died at 30 weeks gestation. Heterozygous family members had normal cardiac function. Fetus also had dysmorphic facial features. PMID: 30046096. An additional case. A consanguineous family of Tunisian decent. 3 year old affected with mixed HCM/DCM and dysmorphic features. PMID: 31074094. An additional case. A family with 6 affected individuals. PMID: 21441111. KO mouse model that replicates the human disease phenotype |
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| Hypertrophic cardiomyopathy v2.10 | ALPK3 | Ivone Leong Publications for gene: ALPK3 were set to 26846950; 27106955; 32480058 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.9 | ALPK3 | Ivone Leong Phenotypes for gene: ALPK3 were changed from Hypertrophic cardiomyopathy to Cardiomyopathy, familial hypertrophic 27, 618052 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v2.4 | ALPK3 |
Zornitza Stark gene: ALPK3 was added gene: ALPK3 was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Expert list Mode of inheritance for gene: ALPK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ALPK3 were set to 26846950; 27106955; 32480058 Phenotypes for gene: ALPK3 were set to Hypertrophic cardiomyopathy Review for gene: ALPK3 was set to GREEN gene: ALPK3 was marked as current diagnostic Added comment: Assessed as Strong by ClinGen (ALPK3-HCM) 4 consanguineous families with ALPK3 biallelic pathogenic variants were identified in 2 papers. 3 families are reported in Alomani (2015) (26846950) and 1 in Phelan (2016) with accompanying functional evidence (27106955). ALPK3 knock out mice develop cardiomyopathy (DCM and HCM) Van Sligtenhorst (2012). A case series of 19 paeditric cardiomyopathy cases with ALPK3 pathogeic variants concluded: Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy. Sources: Expert list |
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