Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000003593 | SCV001524500 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 | 2019-11-06 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Gene |
RCV003128568 | SCV003805616 | pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant creates a TDP1-DNA complex that results in reduced protein activity and altered protein function (Interthal et al., 2005a, Interthal et al. 2005b, Hirano et al. 2007); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21463258, 21246735, 21167187, 22536944, 19883083, 22788692, 25024006, 25111769, 31723605, 24856239, 26601161, 17948061, 19139070, 22214184, 22522093, 23626666, 25841101, 29898404, 16141202, 19211312, 19476377, 21677033, 22155078, 24637157, 16935573, 19139134, 20687496, 20097655, 33425909, 15744309, 24236237, 31429931, 12244316, 31182267, 15920477) |
| Johns Hopkins Genomics, |
RCV000003593 | SCV003927253 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 | 2023-04-20 | criteria provided, single submitter | clinical testing | This TDP1 variant (rs119467003) is absent from a large population dataset and has been reported in ClinVar. The histidine residue at this position is strongly conserved across the vertebrate species assessed. This amino acid substitution (p.His493Arg) changes a key active site residue that serves as a proton donor/acceptor. Functional studies demonstrate that this variant creates a TDP1-DNA covalent intermediate that results in reduced protein activity and altered protein function. This same variant has been detected in a homozygous state in three independent families with SCAN1. We consider c.1478A>G (p.His493Arg) to be pathogenic for autosomal recessive spinocerebellar ataxia with axonal neuropathy-1 (SCAN1). |
| Genomic Medicine Center of Excellence, |
RCV000003593 | SCV005373969 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 | 2024-09-22 | criteria provided, single submitter | clinical testing | |
| Neurogenomics Lab, |
RCV000003593 | SCV005849061 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 | 2025-02-10 | criteria provided, single submitter | research | The highest allele frequency in gnomAD v4.0 is 0.0001335 (10/74916 alleles) in African/African American population). PP3_Strong: REVEL score is 0.95. PS3_Supporting: functional studies provide supportive evidence that the variant has a damaging effect on the gene or gene product (PMID:15920477,16141202). PS4 Met: this variant has been observed in >10 probands with consistent phenotype for disorder. Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/. |
| OMIM | RCV000003593 | SCV000023751 | pathogenic | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 | 2002-10-01 | no assertion criteria provided | literature only |