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| Mendeliome v1.3337 | MDC1 | Zornitza Stark Marked gene: MDC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3337 | MDC1 | Zornitza Stark Gene: mdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3337 | MDC1 | Zornitza Stark Publications for gene: MDC1 were set to PMID: 40954969, 34089056 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3336 | MDC1 | Zornitza Stark Classified gene: MDC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3336 | MDC1 | Zornitza Stark Gene: mdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3316 | MDC1 |
Sarah Milton gene: MDC1 was added gene: MDC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MDC1 were set to PMID: 40954969, 34089056 Phenotypes for gene: MDC1 were set to Oligoasthenoteratozoospermia, MONDO:0850098, MDC1-related Review for gene: MDC1 was set to AMBER Added comment: MDC1 encodes mediator of DNA damage checkpoint I protein. PMID: 40954969 describes 2 affected individuals with biallelic loss of function (nonsense and start loss) variants in MDC1 with reduced sperm count, abnormal morphology and poor motility. 1 family consanguineous. PMID: 34089056 describes 1 similarly affected individual with 2 loss of function variants not confirmed in trans. All adequately rare in gnomad v4. No homozygous NMD predicted variants in gnomad v4. Knockout mice models show meiotic arrest in spermatocytes which subsequently undergo apoptosis. Functional studies performed in PMID:40954969 showed lack of protein in affected patient cells and lack of colocalization usual partner protein. Didn't demonstrate conclusively loss of downstream function. Sources: Literature |
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| Mendeliome v1.532 | TIMMDC1 | Zornitza Stark Classified gene: TIMMDC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.532 | TIMMDC1 | Zornitza Stark Gene: timmdc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.526 | TIMMDC1 | Paul De Fazio reviewed gene: TIMMDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36349561, 33278652; Phenotypes: Mitochondrial complex I deficiency, nuclear type 31 MIM#618251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7358 | JMJD1C |
Zornitza Stark gene: JMJD1C was added gene: JMJD1C was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JMJD1C were set to 26181491; 32996679 Phenotypes for gene: JMJD1C were set to Intellectual disability Review for gene: JMJD1C was set to GREEN Added comment: Reported in ID cohort (with Rett-like phenotypic overlap) with supporting functional studies (PMID: 26181491). 7 individuals with rare variants identified, and variants demonstrated to be de novo in 2, one with a Rett-like phenotype and the other with ID. Functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. JMJD1C protein shown to be widely expressed in brain regions and that its depletion compromised dendritic activity. Splice-disrupting JMJD1C variant reported in association with learning disability and myoclonic epilepsy (PMID 32996679). Disruption of gene due to balanced translocation (PMID 33591602) implicated in autism spectrum disease phenotype. Sources: Expert Review |
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| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Marked gene: TIMMDC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Tag deep intronic tag was added to gene: TIMMDC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Classified gene: TIMMDC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1778 | TIMMDC1 | Zornitza Stark Gene: timmdc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1777 | TIMMDC1 |
Zornitza Stark gene: TIMMDC1 was added gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674; 30981218 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251 Review for gene: TIMMDC1 was set to AMBER Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect. Sources: NHS GMS |
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