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| Ataxia - adult onset v0.140 | SCA12 | Bryony Thompson Marked STR: SCA12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.140 | SCA12 | Bryony Thompson Str: sca12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.140 | SCA12 | Bryony Thompson Classified STR: SCA12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.140 | SCA12 | Bryony Thompson Str: sca12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.139 | SCA12 |
Bryony Thompson STR: SCA12 was added STR: SCA12 was added to Ataxia - adult onset. Sources: Expert list Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA12 were set to 27864267; 33811808 Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326 Review for STR: SCA12 was set to GREEN STR: SCA12 was marked as clinically relevant Added comment: NM_181675.3:c.27CAG[X] Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase Normal: ≤32 repeats Uncertain: ~40-50 repeats have been reported, 43 repeats is the lowest reported in an established affected individual in a family with SCA12 Established pathogenic (used as diagnostic cut-off): ≥51 repeats Sources: Expert list |
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| Ataxia - adult onset v0.138 | Bryony Thompson removed STR:SCA12 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.87 | SCA12 | Bryony Thompson Classified STR: SCA12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.87 | SCA12 | Bryony Thompson Str: sca12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.86 | SCA12 |
Bryony Thompson STR: SCA12 was added STR: SCA12 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to STR: SCA12. Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA12 were set to 29325606; 20301381 Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326 Review for STR: SCA12 was set to GREEN STR: SCA12 was marked as clinically relevant Added comment: NM_181675.3:c.27CAG[X] Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase Normal: ≤32 repeats Reduced penetrance: ~40-66 repeats Full penetrance: ≥66 repeats Sources: Expert list |
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| Ataxia - adult onset v0.85 | SCA10 | Bryony Thompson Classified STR: SCA10 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.85 | SCA10 | Bryony Thompson Str: sca10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.84 | SCA10 |
Bryony Thompson STR: SCA10 was added STR: SCA10 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to STR: SCA10. Mode of inheritance for STR: SCA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA10 were set to 20301354 Phenotypes for STR: SCA10 were set to Spinocerebellar ataxia 10 MIM#603516 STR: SCA10 was marked as clinically relevant Added comment: NM_013236.2:c.1430+54822ATTCT[X] Toxic RNA gain-of-function mechanism of disease Normal alleles: 10-32 ATTCT repeats Alleles of questionable significance: 33-280 ATTCT repeats Reduced-penetrance alleles: 33-850 repeats Full-penetrance alleles: 800-4,500 ATTCT repeats Sources: Expert list |
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| Ataxia - adult onset v0.81 | SCA17 | Bryony Thompson Classified STR: SCA17 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.81 | SCA17 | Bryony Thompson Str: sca17 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.80 | SCA17 |
Bryony Thompson STR: SCA17 was added STR: SCA17 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to STR: SCA17. Mode of inheritance for STR: SCA17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA17 were set to 20301611; 29325606 Phenotypes for STR: SCA17 were set to Spinocerebellar ataxia 17 MIM#607136 Review for STR: SCA17 was set to GREEN STR: SCA17 was marked as clinically relevant Added comment: NM_003194.4:c.172_174[X] Mechanism of disease expected to be gain of function Normal: ≤ 40 CAG/CAA repeats Reduced-penetrance: 41-48 CAG/CAA repeats, individual may or may not develop symptoms. Full-penetrance: ≥49 CAG/CAA repeats Sources: Expert list |
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| Ataxia - adult onset v0.71 | SCA1 | Bryony Thompson Classified STR: SCA1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.71 | SCA1 | Bryony Thompson Str: sca1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.70 | SCA1 |
Bryony Thompson changed review comment from: NM_000332.3:c.589_591CAG[X] Toxic protein aggregation is mechanism of disease Sources: Expert list; to: NM_000332.3:c.589_591CAG[X] Toxic protein aggregation is mechanism of disease Normal: ≤35 CAG repeats or 36-44 CAG repeats with CAT interruptions Mutable normal (intermediate): 36-38 CAG repeats without CAT interruptions Full-penetrance: ≥39 CAG repeats without CAT interruptions or ≥46 uninterrupted CAG repeats with CAT interruptions and additional CAGs Sources: Expert list |
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| Ataxia - adult onset v0.70 | SCA1 |
Bryony Thompson STR: SCA1 was added STR: SCA1 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to STR: SCA1. Mode of inheritance for STR: SCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA1 were set to 29325606; 20301363 Phenotypes for STR: SCA1 were set to Spinocerebellar ataxia 1 MIM#164400 Review for STR: SCA1 was set to GREEN STR: SCA1 was marked as clinically relevant Added comment: NM_000332.3:c.589_591CAG[X] Toxic protein aggregation is mechanism of disease Sources: Expert list |
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| Ataxia - adult onset v0.36 | ATXN1 |
Bryony Thompson changed review comment from: From OMIM: The cause of spinocerebellar ataxia-1 is an expansion of a (CAG)n repeat in the gene encoding ataxin-1 located on 6p. Alleles with 36 to 38 triplets were present in individuals with ataxia but without additional characteristic features of SCA1. SCA1 phenotypes were found for patients with 41 and 43 triplets. Sources: Expert list; to: Adult onset ataxia. From OMIM: The cause of spinocerebellar ataxia-1 is an expansion of a (CAG)n repeat in the gene encoding ataxin-1 located on 6p. Alleles with 36 to 38 triplets were present in individuals with ataxia but without additional characteristic features of SCA1. SCA1 phenotypes were found for patients with 41 and 43 triplets. Sources: Expert list |
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| Ataxia - adult onset v0.35 | ATXN1 |
Bryony Thompson gene: ATXN1 was added gene: ATXN1 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to gene: ATXN1. Mode of inheritance for gene: ATXN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN1 were set to 8358429; 11973625 Phenotypes for gene: ATXN1 were set to Spinocerebellar ataxia 1 MIM#164400 Mode of pathogenicity for gene: ATXN1 was set to Other Review for gene: ATXN1 was set to GREEN Added comment: From OMIM: The cause of spinocerebellar ataxia-1 is an expansion of a (CAG)n repeat in the gene encoding ataxin-1 located on 6p. Alleles with 36 to 38 triplets were present in individuals with ataxia but without additional characteristic features of SCA1. SCA1 phenotypes were found for patients with 41 and 43 triplets. Sources: Expert list |
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| Ataxia - adult onset v0.15 | IFRD1 |
Bryony Thompson gene: IFRD1 was added gene: IFRD1 was added to Ataxia - adult onset. Sources: Literature Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IFRD1 were set to 29362493; 28601596; 19409521 Phenotypes for gene: IFRD1 were set to Spinocerebellar ataxia 18 MIM#607458 Review for gene: IFRD1 was set to RED Added comment: The variant (c.514 A>G, p.I172V) was identified in a 5-generation American family of Irish ancestry with sensorimotor neuropathy with ataxia in two affected individuals sequenced. It is too common (0.3%) for a dominant condition in the African population in gnomAD. The same variant segregated with slowly progressing gait ataxia, pyramidal tract signs and peripheral neuropathy in three siblings from a Chinese family. No functional analyses of the variant has been conducted. A different variant (c.4C>G p.Pro2Ala) in the gene has been identified in a case with isolated palatal tremor, with no ataxia in the case or reported in the family. SCA18 is currently mapped to the genomic region on OMIM, not this gene. Sources: Literature |
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