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| Dilated Cardiomyopathy v0.127 | TTN | Zornitza Stark Publications for gene: TTN were set to 22335739; 25589632; 28045975 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.126 | TTN | Zornitza Stark edited their review of gene: TTN: Added comment: DEFINITIVE by ClinGen.; Changed publications: 22335739, 33947203 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.55 | ILK |
Paul De Fazio changed review comment from: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). 1 patient (Leu53Met) also had a MYBPC3 missense variant variant and 1 (Arg149Gln) also had a TTN frameshift variant. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD).; to: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies, although 1 also had a TTN frameshift variant. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). 1 patient (Leu53Met) also had a MYBPC3 missense variant variant and 1 (Arg149Gln) also had a TTN frameshift variant. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD). |
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| Dilated Cardiomyopathy v0.55 | ILK |
Paul De Fazio changed review comment from: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). The PanelApp GEL review for this gene states that 1 patient had a previously reported MYBPC3 variant and 1 had a TTN frameshift variant, but I can only find evidence in the supp material of the TTN frameshift in the individual with Arg149Gln. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD).; to: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). 1 patient (Leu53Met) also had a MYBPC3 missense variant variant and 1 (Arg149Gln) also had a TTN frameshift variant. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD). |
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| Dilated Cardiomyopathy v0.55 | ILK |
Paul De Fazio changed review comment from: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). The PanelApp GEL review for this gene states that 1 patient had a previously reported MYBPC3 variant and 1 had a TTN frameshift variant, but I'm not sure where this information comes from. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD).; to: Summary: 4 individuals with DCM reported with variants with 3 or fewer hets in gnomAD, mostly in cohort studies. 1 individual with HCM also reported. Red in PanelApp GEL. PMID 17646580: Used zebrafish model to identify novel genes required for myocardial function and found ILK as a candidate. Screening individuals with severe DCM showed a Ala262Val missense variant (absent from gnomAD). Functional studies showed reduced kinase activity for the mutant protein. PMID 27886618: 4 variants identified in a DCM cohort (gnomad: Glu51Gn 3 hets, Leu53Met 122 hets, Arg149Gln 3 hets, Arg349His 27 hets). The PanelApp GEL review for this gene states that 1 patient had a previously reported MYBPC3 variant and 1 had a TTN frameshift variant, but I can only find evidence in the supp material of the TTN frameshift in the individual with Arg149Gln. PMID 25163546: 3 variants identified in a DCM cohort (gnomAD: 18 hets, 269 hets, Absent). 1 missense variant also seen in a HCM cohort (PMID: 26656175; 4 hets in gnomAD). |
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| Dilated Cardiomyopathy v0.43 | CRYAB |
Paul De Fazio changed review comment from: Not curated by ClinGen as of this review. Associated with DCM in OMIM but also myopathy and congenital cataracts (the association with the latter phenotypes is stronger). 3 independent individuals/families with DCM reported that I could find. 1 additional report of RCM. PMID 16793013: 1 heterozygous missense variant in an individual with mild, late-onset DCM (200 patient cohort) PMID 16793013: 1 heterozygous missense variant in a 71-year-old individual with DCM (130 patient cohort). Functional studies showed impared binding to TTN. PMID 23590293: 1 heterozygous stop-loss variant identified in a family with congenital cataracts and DCM, although not all members of the family with the variant had DCM. PMID 29253866: variant identified in an individual with restrictive cardiomyopathy (cohort study) Amber in PanelApp GEL I don't think there's sufficient evidence for an association with DCM so I am marking this red.; to: Not curated by ClinGen as of this review. Associated with DCM in OMIM but also myopathy and congenital cataracts (the association with the latter phenotypes is stronger). 3 independent individuals/families with DCM reported that I could find. 1 additional report of RCM. PMID 16793013: 1 heterozygous missense variant in an individual with mild, late-onset DCM (200 patient cohort) (253 hets in gnomAD) PMID 16483541: 1 heterozygous missense variant in a 71-year-old individual with DCM (130 patient cohort). Functional studies showed impared binding to TTN (18 hets in gnomad). PMID 23590293: 1 heterozygous stop-loss variant identified in a family with congenital cataracts and DCM, although not all members of the family with the variant had DCM. PMID 29253866: variant identified in an individual with restrictive cardiomyopathy (cohort study) Amber in PanelApp GEL I don't think there's sufficient evidence for an association with DCM so I am marking this red. |
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| Dilated Cardiomyopathy v0.25 | TTN | Zornitza Stark reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 22335739; Phenotypes: Cardiomyopathy, dilated, 1G, MIM#604145; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.25 | TTN | Zornitza Stark Marked gene: TTN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.25 | TTN | Zornitza Stark Gene: ttn has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.25 | TTN | Zornitza Stark Publications for gene: TTN were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.24 | TTN | Zornitza Stark Phenotypes for gene: TTN were changed from to Cardiomyopathy, dilated, 1G, MIM#604145 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.23 | TTN | Zornitza Stark Mode of inheritance for gene: TTN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.22 | TTN | Elena Savva reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25589632, 28045975; Phenotypes: Cardiomyopathy, dilated, 1G, 604145, Cardiomyopathy, familial hypertrophic, 9, 613765, Muscular dystrophy, limb-girdle, autosomal recessive 10, 608807, (LGMDR10), Myopathy, myofibrillar, 9, with early respiratory failure, 603689, Salih myopathy, 611705, Tibial muscular dystrophy, tardive, 600334; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy v0.0 | TTN |
Zornitza Stark gene: TTN was added gene: TTN was added to Dilated cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: TTN was set to Unknown |
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