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| Intellectual disability - microarray and sequencing v5.117 | RNF13 | Arina Puzriakova Phenotypes for gene: RNF13 were changed from Cortical visual impairment; Epileptic encephalopathy, early infantile, 73, 618379; Failure to thrive; Seizures; Congenital microcephaly; Abnormal muscle tone; Feeding difficulties; Intellectual disability; Global developmental delay; Sensorineural hearing impairment to Developmental and epileptic encephalopathy 73, OMIM:618379 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1510 | RNF13 |
Arina Puzriakova Tag watchlist was removed from gene: RNF13. Tag for-review was removed from gene: RNF13. |
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| Intellectual disability - microarray and sequencing v3.1510 | RNF13 | Sarah Leigh commented on gene: RNF13: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1509 | RNF13 |
Arina Puzriakova Source Expert Review Green was added to RNF13. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.478 | RNF13 | Arina Puzriakova Classified gene: RNF13 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.478 | RNF13 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.478 | RNF13 | Arina Puzriakova Gene: rnf13 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.477 | RNF13 | Arina Puzriakova Tag for-review tag was added to gene: RNF13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.24 | RNF13 | Sarah Leigh Classified gene: RNF13 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.24 | RNF13 | Sarah Leigh Gene: rnf13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.23 | RNF13 |
Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive functional studies.; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive functional studies. Gain-of-function mechanism has been reported, therefore the mutational spectrum may be limited and is still to be determined through further cases or further functional studies (view of Helen Britain, GeL Clincial Fellow). |
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| Intellectual disability - microarray and sequencing v3.15 | RNF13 | Sarah Leigh reviewed gene: RNF13: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.3 | RNF13 | Zornitza Stark reviewed gene: RNF13: Rating: GREEN; Mode of pathogenicity: None; Publications: 30595371; Phenotypes: Epileptic encephalopathy, early infantile, 73, MIM# 618379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.981 | RNF13 | Catherine Snow Tag watchlist tag was added to gene: RNF13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.978 | RNF13 |
Catherine Snow Source Expert Review was added to RNF13. Source Expert Review Amber was added to RNF13. Added phenotypes Epileptic encephalopathy, early infantile, 73, 618379 for gene: RNF13 Publications for gene RNF13 were changed from to 30595371 Rating Changed from No List (delete) to Amber List (moderate evidence) |
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| Intellectual disability - microarray and sequencing v2.789 | RNF135 | Louise Daugherty Publications for gene: RNF135 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.788 | RNF135 | Louise Daugherty Classified gene: RNF135 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.788 | RNF135 | Louise Daugherty Gene: rnf135 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.620 | RNF135 | Konstantinos Varvagiannis reviewed gene: RNF135: Rating: RED; Mode of pathogenicity: None; Publications: 30665703, 17632510, 26368817; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.588 | RNF13 |
Konstantinos Varvagiannis gene: RNF13 was added gene: RNF13 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RNF13 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: RNF13 were set to Congenital microcephaly; Feeding difficulties; Failure to thrive; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Cortical visual impairment; Sensorineural hearing impairment Penetrance for gene: RNF13 were set to unknown Mode of pathogenicity for gene: RNF13 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: RNF13 was set to GREEN Added comment: Edvardson et al. (doi.org/10.1016/j.ajhg.2018.11.018) report on 3 unrelated individuals with heterozygous de novo missense RNF13 variants. Features included (rather borderline) congenital microcephaly, feeding difficulties, tone abnormalities, DD/ID (3/3), seizures (3/3), hearing loss and cortical visual impairment. One individual harbored the p.Leu311Ser variant while 2 others the p.Leu312Pro. RNF13 encodes a protein known to interact and activate IRE1a, an endoplasmatic reticulum (ER) stress sensor. The 2 variants are predicted in silico not to affect the tertiary structure of the protein. Further to this, RNF13 is tolerant to LoF variants (pLI of 0 in ExAC). Therefore a gain-of-function mechanism was hypothesized for the 2 missense variants and demonstrated for the Leu311Ser: - Protein levels were similar to controls upon Western blotting in patient fibroblasts. - Enhanced IRE1a activation was demonstrated in patient cells when compared to controls, confirming gain-of-function. - Increased activation (/ER stress), in turn, resulted in abnormally increased apoptosis similarly to what is observed in other neurological disorders. Fibroblast/lymphoblast cells were not available from individuals with the Leu312Pro variant although a similar mechanism is presumed. Although neurodegeneration is suggested by the above pathophysiologic mechanism, this is manifested by failure to achieve milestones (rather than eg. regression after a normal period of postnatal development / loss of milestones). --------- RNF13 is not associated with any phenotype in OMIM, nor in G2P. This gene is not commonly included in gene panels for ID offered by diagnostic laboratories. --------- As a result, RNF13 can be considered for inclusion in this panel possibly as green (or amber). Sources: Literature |
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| Intellectual disability - microarray and sequencing v2.468 | RNF135 | Louise Daugherty Source Victorian Clinical Genetics Services was added to RNF135. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RNF135 | BRIDGE consortium edited their review of RNF135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RNF135 | Louise Daugherty classified RNF135 as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RNF135 | Louise Daugherty commented on RNF135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RNF135 | BRIDGE consortium reviewed RNF135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||