Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
13 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.10 | MYLK3 |
Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: MYLK3. Tag Q2_25_expert_review was removed from gene: MYLK3. Tag Q2_25_ NHS_review was removed from gene: MYLK3. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.10 | MYLK3 | Achchuthan Shanmugasundram commented on gene: MYLK3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.1 | MYLK3 | Matthew Edwards Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.1 | MYLK3 |
Matthew Edwards edited their review of gene: MYLK3: Added comment: Several mouse models (and a zebrafish), one of which is heterozygous KO which recapitulates DCM (31244672). Good expression/protein interaction evidence 17885681, 18202317) Rare cases in literature - PMID: 29235529 has two families: Family A - two early onset sibs and their affected mother (later onset) had heterozygous MYLK3 LOF variant - sibs also had a FLNC LOF variant (from unaffected father), likely explaining early onset. Family B two later onset sibs with heterozygous MYLK3 LOF variant. functional studies of both showed reduced protein expression. PMID: 30690923: has proband with heterozygous LOF variant. 3 consanguineous families with hom LOf (2 families) and hom missense (1 family). We've seen 10 LOF variants in DCM patients (with 3 detected in control set of non-DCM cases ~5000 samples - one possibly too young for phenotype, 2 with variant in only one of two isforms expressed in heart), but currently classify as VUS due to limited haploinsufficiency evidence. (Clin~Gen curation still pending); Changed rating: GREEN |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.1 | MYLK3 | Arina Puzriakova commented on gene: MYLK3: Tagged for GMS review to determine whether this gene should remain Amber or be promoted to Green. As stated by Matthew Edwards, the evidence is borderline - several unrelated cases and supportive mouse model but MOI varies, one family also had variants in another DCM gene and there are unaffected carriers. MYLK3 is green on the R135 Paediatric or syndromic cardiomyopathy panel based on the same evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.1 | MYLK3 |
Arina Puzriakova Tag Q2_25_ promote_green tag was added to gene: MYLK3. Tag Q2_25_expert_review tag was added to gene: MYLK3. Tag Q2_25_ NHS_review tag was added to gene: MYLK3. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v3.1 | MYLK3 | Matthew Edwards reviewed gene: MYLK3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17885681, 31244672, 37128901, 32213617, 29235529, 30690923; Phenotypes: Dilated Cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v2.4 | MYLK3 | Arina Puzriakova Tag Q2_21_rating was removed from gene: MYLK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v2.4 | MYLK3 | Arina Puzriakova reviewed gene: MYLK3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v1.26 | MYLK3 | Arina Puzriakova Tag gene-checked tag was added to gene: MYLK3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v1.22 | MYLK3 | Ivone Leong Classified gene: MYLK3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v1.22 | MYLK3 | Ivone Leong Gene: mylk3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated and arrhythmogenic cardiomyopathy v1.21 | MYLK3 |
Ivone Leong gene: MYLK3 was added gene: MYLK3 was added to Dilated cardiomyopathy - adult and teen. Sources: Literature Q2_21_rating tags were added to gene: MYLK3. Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709; 30690923 Phenotypes for gene: MYLK3 were set to Dilated cardiomyopathy, MONDO:0005021 Review for gene: MYLK3 was set to GREEN Added comment: This gene is also on the Cardiomyopathies - including childhood onset (Version 1.35) as an Amber gene with a recommendation of promoting to Green. This gene is not associated with a phenotype on OMIM or Gene2Phenotype. PMID: 29235529 describes 2 families with heterozygous variant in this gene. Family A - 2 sibs diagnosed with DCM at 9 and 10 months of age and affected mother diagnosed with DCM at 40 yo. As the children had a more severe phenotype and earlier onset than the mother the authors did further analysis and found the sibs had an additional variant in FLNC, which is also linked to DCM. The authors suggest this additional variant could account for the more severe phenotype in the children. Family B - 2 brothers diagnosed with DCM at 56 and 52 yo, both have a heterozygous frameshift variant in this gene. Mother and sister had died young and DCM diagnosis is inconclusive. PMID: 30690923 describes another case. Proband has a heterozygous frameshift variant in this gene. Rest of the family have no cardiac phenotype and no variants in this gene except for one daughter. Daughter has the same variant and has dilation of LV and ST-T abnormalities but these do not meet the criteria for DCM. PMID: 32870709 describes three consanguineous families with homozygous variants in this gene. Review from Zornitza Stark: "Rating: I don't know Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models. Sources: Literature Created: 16 Apr 2021, 9:24 a.m." There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||