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| Ataxia and cerebellar anomalies - narrow panel v4.38 | SPTAN1 | Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: SPTAN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.37 | SPTAN1 | Eleanor Williams reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.35 | SPTAN1 |
Achchuthan Shanmugasundram Source Expert Review Green was added to SPTAN1. Source NHS GMS was added to SPTAN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Ataxia and cerebellar anomalies - narrow panel v4.29 | SPTAN1 | Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Although there are three unrelated cases reported with biallelic SPTAN1 variants and hereditary spastic paraplegia, they do not present with ataxia (PMID:31515523; PMID:34526651). Hence, the MOI should remain as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted". | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.29 | SPTAN1 | Achchuthan Shanmugasundram Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.28 | SPTAN1 | Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064 to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.35 | SPTAN1 |
Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model. One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum. In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, 3 were presented with complex HA/HSP and two were presented with pure HA. A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia. In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.; to: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model. One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum. In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA. A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia. In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia. |
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| Ataxia and cerebellar anomalies - narrow panel v3.35 | SPTAN1 | Achchuthan Shanmugasundram Phenotypes for gene: SPTAN1 were changed from Ataxia; hereditary spastic paraplegia to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.34 | SPTAN1 | Achchuthan Shanmugasundram Publications for gene: SPTAN1 were set to 36331550; 35150594 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.33 | SPTAN1 | Achchuthan Shanmugasundram edited their review of gene: SPTAN1: Changed phenotypes to: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437, Hereditary spastic paraplegia, MONDO:0019064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.33 | SPTAN1 | Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.33 | SPTAN1 | Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.33 | SPTAN1 | Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.32 | SPTAN1 | Achchuthan Shanmugasundram reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29050398, 30548380, 33790315, 34590414, 35150594, 36331550, 36408834; Phenotypes: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.18 | SPTAN1 |
Dmitrijs Rots gene: SPTAN1 was added gene: SPTAN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to 36331550; 35150594 Phenotypes for gene: SPTAN1 were set to Ataxia; hereditary spastic paraplegia Review for gene: SPTAN1 was set to GREEN Added comment: Two large cohorts (36331550; 35150594) described >30 cases with hereditary ataxia and a variant in SPTAN1. Sources: Literature |
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