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Hereditary neuropathy or pain disorder v7.23 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v7.23 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least three different variants reported (two published variants including the founder-variant from the Middle East) in five unrelated families including the Sheffield case. There is also sufficient functional evidence available in support of the p.His493Arg founder variant. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v7.23 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v7.22 TDP1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM accessed 24 October 2025.
Hereditary neuropathy or pain disorder v7.22 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250 to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, MONDO:0011801
Hereditary neuropathy or pain disorder v7.21 TDP1 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: TDP1.
Hereditary neuropathy or pain disorder v7.21 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed before, PMID:31182267 reported three unrelated probands (two Omani families and one Saudi Arabian family) with homozygous missense variant in TDP1 gene - p.His493Arg, which has been confirmed by haplotype analysis as a founder variant. However, the allele count for this variant in gnomAD v4.1.0 is 13 and it is not found in homozygous state in any of those individuals. In addition, there is also function evidence available that showed that cells expressing TDP1 gene with H493R variant promotes mitochondrial dysfunction and mitophagy.

PMID:39576382 reported a female patient from a Pakistani family with autosomal recessive spinocerebellar ataxia with axonal neuropathy type 1, who presented with additional clinical features including congenital onset of disease, This patient was identified with novel missense variant in TDP1 - p.His478Tyr. via WES and autosomal recessive segregation was confirmed by Sanger sequencing. The allele count for this variant in gnomAD v4.1.0 is 10, of which eight were from South Asian ancestry - however, it is absent in homozygous state in the database.

As reviewed by Ian Berry and Lauren Turton, there is an additional case reported in with p.His493Arg variant and a likely LoF splicing variant, who had early adulthood onset progressive ataxia and axonal neuropathy.; to: As reviewed before, PMID:31182267 reported three unrelated probands (two Omani families and one Saudi Arabian family) with homozygous missense variant in TDP1 gene - p.His493Arg, which has been confirmed by haplotype analysis as a founder variant. However, the allele count for this variant in gnomAD v4.1.0 is 13 and it is not found in homozygous state in any of those individuals. In addition, there is also functional evidence available that showed that cells expressing TDP1 gene with H493R variant promotes mitochondrial dysfunction and mitophagy.

PMID:39576382 reported a female patient from a Pakistani family with autosomal recessive spinocerebellar ataxia with axonal neuropathy type 1, who presented with additional clinical features including congenital onset of disease. This patient was identified with a novel missense variant in TDP1 (p.His478Tyr) via WES, and autosomal recessive segregation was confirmed by Sanger sequencing. The allele count for this variant in gnomAD v4.1.0 is 10, of which eight were from South Asian ancestry - however, it is absent in homozygous state in the database.

As reviewed by Ian Berry and Lauren Turton, there is an additional case reported in with p.His493Arg variant and a likely LoF splicing variant, who had early adulthood onset progressive ataxia and axonal neuropathy.
Hereditary neuropathy or pain disorder v7.13 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Added comment: As reviewed before, PMID:31182267 reported three unrelated probands (two Omani families and one Saudi Arabian family) with homozygous missense variant in TDP1 gene - p.His493Arg, which has been confirmed by haplotype analysis as a founder variant. However, the allele count for this variant in gnomAD v4.1.0 is 13 and it is not found in homozygous state in any of those individuals. In addition, there is also function evidence available that showed that cells expressing TDP1 gene with H493R variant promotes mitochondrial dysfunction and mitophagy.

PMID:39576382 reported a female patient from a Pakistani family with autosomal recessive spinocerebellar ataxia with axonal neuropathy type 1, who presented with additional clinical features including congenital onset of disease, This patient was identified with novel missense variant in TDP1 - p.His478Tyr. via WES and autosomal recessive segregation was confirmed by Sanger sequencing. The allele count for this variant in gnomAD v4.1.0 is 10, of which eight were from South Asian ancestry - however, it is absent in homozygous state in the database.

As reviewed by Ian Berry and Lauren Turton, there is an additional case reported in with p.His493Arg variant and a likely LoF splicing variant, who had early adulthood onset progressive ataxia and axonal neuropathy.; Changed rating: GREEN; Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605, 39576382; Changed phenotypes to: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, MONDO:0011801
Hereditary neuropathy or pain disorder v7.8 TDP1 Lauren Turton reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia with axonal neuropathy (OMIM: 607250); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary neuropathy or pain disorder v6.161 TDP1 Sarah Leigh Added comment: Comment on publications: PMID: 39576382 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Hereditary neuropathy or pain disorder v6.161 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Added comment: Comment on list classification: This gene remains amber, as there are only two disease associated variants have been reported (PMID: 12244316;31182267;39576382)
Hereditary neuropathy or pain disorder v6.160 TDP1 Sarah Leigh Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.159 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Hereditary neuropathy or pain disorder v6.157 TDP1 Sarah Leigh reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39576382; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, MONDO:0011801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.157 TDP1 Sarah Leigh Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary neuropathy or pain disorder v6.148 CTDP1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CTDP1.
Tag Q3_24_NHS_review was removed from gene: CTDP1.
Hereditary neuropathy or pain disorder v6.148 CTDP1 Sarah Leigh commented on gene: CTDP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v6.147 CTDP1 Sarah Leigh Source Expert Review Green was added to CTDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.38 CTDP1 Sarah Leigh Phenotypes for gene: CTDP1 were changed from Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) to Congenital cataracts, facial dysmorphism, and neuropathy, OMIM:604168; congenital cataracts-facial dysmorphism-neuropathy syndrome, MONDO:0011402
Hereditary neuropathy or pain disorder v6.20 CTDP1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CTDP1.
Tag Q3_24_NHS_review tag was added to gene: CTDP1.
Hereditary neuropathy or pain disorder v6.20 CTDP1 Sarah Leigh reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 15322984, 20301787, 10439962, 29174527, 14517542, 16194727, 24690360, 21824574, 23408394; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, OMIM:604168, congenital cataracts-facial dysmorphism-neuropathy syndrome, MONDO:0011402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v5.19 CTDP1 Alexander Rossor reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10439962: 29174527: 21824574; Phenotypes: cataratcs, facial dysmorphism, peripheral neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.5 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TDP1.
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from Hereditary Neuropathies to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary neuropathy or pain disorder v3.3 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316
Hereditary neuropathy or pain disorder v3.2 TDP1 Achchuthan Shanmugasundram reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12244316, 31182267; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.2 TDP1 Ian Berry reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12244316, PMID: 31182267; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary neuropathy or pain disorder v0.44 CTDP1 Louise Daugherty commented on gene: CTDP1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype (dysmorphic, cataract) - founder mutation in Roma populations, intronic
Hereditary neuropathy or pain disorder v0.44 CTDP1 Louise Daugherty Classified gene: CTDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v0.44 CTDP1 Louise Daugherty Gene: ctdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v0.1 TDP1 Ellen McDonagh gene: TDP1 was added
gene: TDP1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Red,South West GLH
Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP1 were set to 12244316
Phenotypes for gene: TDP1 were set to Hereditary Neuropathies
Hereditary neuropathy or pain disorder v0.1 CTDP1 Ellen McDonagh gene: CTDP1 was added
gene: CTDP1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Red,South West GLH
Mode of inheritance for gene: CTDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTDP1 were set to 16194727; 24690360; 14517542
Phenotypes for gene: CTDP1 were set to Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN)