PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
11 actions
Mendeliome v1.3656 KLF13 Krithika Murali gene: KLF13 was added
gene: KLF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KLF13 were set to Congenital heart disease MONDO:0005453 - KLF13-related; Dilated cardiomyopathy - MONDO:0005021, KLF13-related
Review for gene: KLF13 was set to AMBER
Added comment: Curated by ClinGen as Moderate for association with congenital heart disease (12/2/2024)

PMID: 33215447 Wang et al 2020 - novel heterozygous variation, NM_015995.3: c.370G>T; p.(Glu124*), co-segregating with congenital heart disease in a 3-generation Chinese family. Supportive functional evidence.

PMID: 35369534 Abhinav et al 2022 - NM_015995.3: c.430G>T; p.(Glu144*) co-segregated with congenital heart disease in a Han Chinese family. Supportive functional evidence.

PMID: 32293321 Li et al 2020 - Two heterozygous missense variants in two unrelated patients with congenital heart disease. However, they have much higher gnomAD frequencies - c.487C > T (P163S) (11 hets gnomAD v4) and c.467G > A (S156N)(22 hets gnomAD v4). No segregation information and the functional evidence was not convincing. This paper was included as genetic evidence in the ClinGen curation.

Monoallelic variants have also been reported in association with adult-onset DCM.

PMID 36346048 Guo et al 2022 – Identified heterozygous KLF13 gene variants co-segregating with adult-onset DCM in 3 unrelated families - c.430G>T (p.E144X); c.580G>T (p.E194X) and c.595T>C (p.C199R). Functional studies support disrupted synergistic transactivation between mutant KLF13 and target genes ACTC1, MYH7 and GATA4. Monoallelic variants in KLF13 have also been associated with congenital heart disease. Of note, 2 individuals from Family 1 and 1 individual from Family 2 also had an atrial septal defect.

PMID 41201692 Tang et al 2025 – report a novel heterozygous truncating KLF13 mutation, i.e., NM_015995.3:c.534 C>G;p.(Tyr178) in two unrelated patients with adult onset DCM (42-year-old male patient and a 51-year old female case 51 years old). Variant was absent in healthy controls. No segregation evidence. Supportive functional evidence.

More evidence including segregation information, genotype-phenotype correlation between DCM and/or congenital heart disease and ascertainment from diverse ancestries required.
Sources: Literature
Mendeliome v1.790 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Mendeliome v1.790 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Mendeliome v1.790 ACTC1 Zornitza Stark Classified gene: ACTC1 as Green List (high evidence)
Mendeliome v1.790 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Mendeliome v1.789 ACTC1 Zornitza Stark reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 5 MIM#612794, Cardiomyopathy, dilated, 1R MIM#613424, Cardiomyopathy, hypertrophic, 11 MIM#612098, ACTC1 related distal arthrogryposis MONDO:0019942; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.776 ACTC1 Lilian Downie gene: ACTC1 was added
gene: ACTC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to PMID: 36945405
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5 MIM#612794; Cardiomyopathy, dilated, 1R MIM#613424; Cardiomyopathy, hypertrophic, 11 MIM#612098; ACTC1 related distal arthrogryposis MONDO:0019942
Review for gene: ACTC1 was set to GREEN
Added comment: ClinGen definitive association with HCM, moderate for DCM
5 new families (8 individuals) with a distral arthrogryposis phenotype (PMID: 36945405)
multiple congenital contractures, neck pterygia, scoliosis, and congenital heart defects/cardiomyopathy
facial features: microretrognathia, ptosis, downslanting palpebral fissures, low-set ears, and a long nasal bridge
All missense variants
Sources: Literature
Mendeliome v0.9545 Zornitza Stark removed gene:ACTC1 from the panel
Mendeliome v0.9537 ACTC1 Krithika Murali gene: ACTC1 was added
gene: ACTC1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to 26061005; 17947298; 31430208; 18403758; 30384889
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5, MIM# 612794; Cardiomyopathy, dilated, 1R - MIM# 613424; Cardiomyopathy, hypertrophic, 11 - #612098
Review for gene: ACTC1 was set to GREEN
Added comment: Four families reported with congenital heart disease and variants in this gene. Note gene is also associated with cardiomyopathies, including paediatric-onset dilated and hypertrophic cardiomyopathy.
Sources: Expert list, Literature
Mendeliome v0.9482 Zornitza Stark removed gene:ACTC1 from the panel
Mendeliome v0.9467 ACTC1 Krithika Murali gene: ACTC1 was added
gene: ACTC1 was added to Mendeliome. Sources: Literature,Expert list
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to 17947298; 31430208
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5 - MIM# 612794; Cardiomyopathy, dilated, 1R - MIM# 613424; Cardiomyopathy, hypertrophic, 11 - #612098; Left ventricular noncompaction 4 - #613424
Review for gene: ACTC1 was set to GREEN
Added comment: Three families reported with congenital heart disease and variants in this gene. Gene is also associated with cardiomyopathies, including paediatric onset.
Sources: Literature, Expert list