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Intellectual disability v9.253 RSF1 Ida Ertmanska Phenotypes for gene: RSF1 were changed from Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.252 RSF1 Ida Ertmanska changed review comment from: PMID: 41606215 Jost et al., 2026
Report of 11 unrelated individuals harboring de novo or inherited from a symptomatic parent heterozygous variants in RSF1 (only 7 with detailed information). All individuals had an NDD: intellectual disability, autism spectrum disorder or developmental delay. Seq method: Exome seq / Genome Seq. 6 variants de novo, one inherited from mosaic mother. Phenotypic spectrum: ID 4/7 (3 mild and 1 moderate-severe), educational difficulties 7/7, seizures 2/7, ASD 3/7, extremities anomalies 4/7, variable skin defects 5/7, variable ophthalmological anomalies 3/7, and other.

RSF1 is linked to AD Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM:620489 in OMIM (accessed 10th Feb 2026). It is not yet listed in ClinGen or Gene2Phenotype.
Sources: Literature; to: PMID: 41606215 Jost et al., 2026
Report of 11 unrelated individuals harboring de novo or inherited from a symptomatic parent heterozygous variants in RSF1 (only 7 with detailed information). All individuals had an NDD: intellectual disability, autism spectrum disorder or developmental delay. Seq method: Exome seq / Genome Seq. 6 variants de novo, one inherited from mosaic mother. Phenotypic spectrum: ID 4/7 (3 mild and 1 moderate-severe), educational difficulties 7/7, seizures 2/7, ASD 3/7, extremities anomalies 4/7, variable skin defects 5/7, variable ophthalmological anomalies 3/7, and other.

RSF1 is not yet linked to disease in OMIM, ClinGen or Gene2Phenotype (resources accessed 10th Feb 2026).
Sources: Literature
Intellectual disability v9.252 RSF1 Ida Ertmanska edited their review of gene: RSF1: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.252 RSF1 Ida Ertmanska Classified gene: RSF1 as Amber List (moderate evidence)
Intellectual disability v9.252 RSF1 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 individuals reported in literature with heterozygous RSF1 variants and syndromic intellectual disability / developmental delay. Based on available evidence, this gene should be promoted to Green for Intellectual disability.
Intellectual disability v9.252 RSF1 Ida Ertmanska Gene: rsf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.251 RSF1 Ida Ertmanska gene: RSF1 was added
gene: RSF1 was added to Intellectual disability. Sources: Literature
Q1_26_promote_green tags were added to gene: RSF1.
Mode of inheritance for gene: RSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RSF1 were set to 41606215
Phenotypes for gene: RSF1 were set to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489
Review for gene: RSF1 was set to GREEN
Added comment: PMID: 41606215 Jost et al., 2026
Report of 11 unrelated individuals harboring de novo or inherited from a symptomatic parent heterozygous variants in RSF1 (only 7 with detailed information). All individuals had an NDD: intellectual disability, autism spectrum disorder or developmental delay. Seq method: Exome seq / Genome Seq. 6 variants de novo, one inherited from mosaic mother. Phenotypic spectrum: ID 4/7 (3 mild and 1 moderate-severe), educational difficulties 7/7, seizures 2/7, ASD 3/7, extremities anomalies 4/7, variable skin defects 5/7, variable ophthalmological anomalies 3/7, and other.

RSF1 is linked to AD Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM:620489 in OMIM (accessed 10th Feb 2026). It is not yet listed in ClinGen or Gene2Phenotype.
Sources: Literature
Intellectual disability v9.144 MED12L Eleanor Williams changed review comment from: Since the last review additional cases have been reported.
In OMIM this gene is associated with Nizon-Isidor syndrome, OMIM:618872 (AD) - accessed 21st October 2025
In ClinGen the gene has a definitive rating with Nizon-Isidor syndrome, MONDO:0030030

There are now 3 more reports of plausable pathogenic variants in this gene in patients with an intellectual disability phenotype. 2 cases with de novo variants and 1 with a maternally inherited variant.

PMID: 36212160 - Park et al 2022 - WES to analyse 1,180 Korean patients with neurological symptoms. 1 individual with a de novo variant c.1895C>T; p.Ser632Leu in MED12L and a phenotype of global developmental delay and facial dysmorphism.

PMID: 35920825 - Ferraz et al 2022 - a male proband with a confirmed de novo germline frameshift variant in MED12L (NM_053002.6 (MED12L_v001):c.971del;p.(pro324Glnfs∗18)) identified by WES. The clinical phenotype included mild motor and speech delay, oligodontia, and dysmorphic signs. Of note the patient also carried 2 de novo chromosomal balanced reciprocal translocations: 46,XY,t(1;2)(p33;p22),t(5;9)(p15;q21) and the authors note that Nizon et al. 2019 report a patient with a balanced reciprocal translocation suggesting that the MED12L loss-of-function variant may contribute to chromosomal instability.

PMID: 40957966 - Dutta et al 2025 - report a proband with likely pathogenic MED12L nonsense variant (p.Arg1210Ter) which is maternally inherited (father also sequenced). At 2.5 yo the proband was diagnosed with global developmental delay, absent speech, ASD, hyperactivity, exophoria and myopia. Developmental regression began between 18 - 24 months. She has frequent respiratory infections. The 19 yo mother has a clinical history which includes speech delay and learning disability, but features are much milder than the proband. The proband also has inherited a pathogenic GAMT variant from her mother and a pathogenic TNFRSF13B variant from her father but these are not thought to contribute to the ID phenotype.; to: Since the last review additional cases have been reported.
In OMIM this gene is associated with Nizon-Isidor syndrome, OMIM:618872 (AD) - accessed 21st October 2025
In ClinGen the gene has a definitive rating with Nizon-Isidor syndrome, MONDO:0030030 (last curated November 19th, 2024)

There are now 3 more reports of plausable pathogenic variants in this gene in patients with an intellectual disability phenotype. 2 cases with de novo variants and 1 with a maternally inherited variant.

PMID: 36212160 - Park et al 2022 - WES to analyse 1,180 Korean patients with neurological symptoms. 1 individual with a de novo variant c.1895C>T; p.Ser632Leu in MED12L and a phenotype of global developmental delay and facial dysmorphism.

PMID: 35920825 - Ferraz et al 2022 - a male proband with a confirmed de novo germline frameshift variant in MED12L (NM_053002.6 (MED12L_v001):c.971del;p.(pro324Glnfs∗18)) identified by WES. The clinical phenotype included mild motor and speech delay, oligodontia, and dysmorphic signs. Of note the patient also carried 2 de novo chromosomal balanced reciprocal translocations: 46,XY,t(1;2)(p33;p22),t(5;9)(p15;q21) and the authors note that Nizon et al. 2019 report a patient with a balanced reciprocal translocation suggesting that the MED12L loss-of-function variant may contribute to chromosomal instability.

PMID: 40957966 - Dutta et al 2025 - report a proband with likely pathogenic MED12L nonsense variant (p.Arg1210Ter) which is maternally inherited (father also sequenced). At 2.5 yo the proband was diagnosed with global developmental delay, absent speech, ASD, hyperactivity, exophoria and myopia. Developmental regression began between 18 - 24 months. She has frequent respiratory infections. The 19 yo mother has a clinical history which includes speech delay and learning disability, but features are much milder than the proband. The proband also has inherited a pathogenic GAMT variant from her mother and a pathogenic TNFRSF13B variant from her father but these are not thought to contribute to the ID phenotype.
Intellectual disability v9.141 MED12L Eleanor Williams edited their review of gene: MED12L: Added comment: Since the last review additional cases have been reported.
In OMIM this gene is associated with Nizon-Isidor syndrome, OMIM:618872 (AD) - accessed 21st October 2025
In ClinGen the gene has a definitive rating with Nizon-Isidor syndrome, MONDO:0030030

There are now 3 more reports of plausable pathogenic variants in this gene in patients with an intellectual disability phenotype. 2 cases with de novo variants and 1 with a maternally inherited variant.

PMID: 36212160 - Park et al 2022 - WES to analyse 1,180 Korean patients with neurological symptoms. 1 individual with a de novo variant c.1895C>T; p.Ser632Leu in MED12L and a phenotype of global developmental delay and facial dysmorphism.

PMID: 35920825 - Ferraz et al 2022 - a male proband with a confirmed de novo germline frameshift variant in MED12L (NM_053002.6 (MED12L_v001):c.971del;p.(pro324Glnfs∗18)) identified by WES. The clinical phenotype included mild motor and speech delay, oligodontia, and dysmorphic signs. Of note the patient also carried 2 de novo chromosomal balanced reciprocal translocations: 46,XY,t(1;2)(p33;p22),t(5;9)(p15;q21) and the authors note that Nizon et al. 2019 report a patient with a balanced reciprocal translocation suggesting that the MED12L loss-of-function variant may contribute to chromosomal instability.

PMID: 40957966 - Dutta et al 2025 - report a proband with likely pathogenic MED12L nonsense variant (p.Arg1210Ter) which is maternally inherited (father also sequenced). At 2.5 yo the proband was diagnosed with global developmental delay, absent speech, ASD, hyperactivity, exophoria and myopia. Developmental regression began between 18 - 24 months. She has frequent respiratory infections. The 19 yo mother has a clinical history which includes speech delay and learning disability, but features are much milder than the proband. The proband also has inherited a pathogenic GAMT variant from her mother and a pathogenic TNFRSF13B variant from her father but these are not thought to contribute to the ID phenotype.; Changed rating: GREEN; Changed publications to: 31155615, 36212160, 35920825, 40957966; Changed phenotypes to: Nizon-Isidor syndrome, OMIM:618872, Nizon-Isidor syndrome, MONDO:0030030; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SRSF1.
Intellectual disability v6.11 SRSF1 Sarah Leigh reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.10 SRSF1 Achchuthan Shanmugasundram Source Expert Review Green was added to SRSF1.
Source NHS GMS was added to SRSF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Classified gene: SRSF1 as Amber List (moderate evidence)
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Gene: srsf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SRSF1.
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram gene: SRSF1 was added
gene: SRSF1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRSF1 were set to 37071997
Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489
Review for gene: SRSF1 was set to GREEN
Added comment: There are 17 individuals from 16 different families were reported with 15 different monoallelic variants (mostly de novo) in SRSF1 gene. They were reported with a neurodevelopmental disorder mainly comprising neurological abnormalities such as intellectual disability/ developmental delay, motor delay, speech delay, and behavioural disorders and facial dysmorphisms. Intellectual disability was present in 16 of 17 individuals (3 severe, 2 moderate, 3 mild to moderate, 3 mild, 1 borderline and 4 unknown severity), while the remaining one had learning disability.

Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS.

This gene has already been associated with neurodevelopmental disorder in both OMIM (MIM #620489) and Gene2Phenotype ('limited' rating in the DD panel).
Sources: Literature