ClinVar Miner

Submissions for variant NM_001130438.3(SPTAN1):c.466C>T (p.Arg156Ter)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV003391174 SCV004101786 likely pathogenic Neuronopathy, distal hereditary motor, autosomal dominant 11; Developmental delay with or without epilepsy 2023-11-14 criteria provided, single submitter clinical testing The variant c.466C>T (p.(Arg156*)) in exon 4 of the SPTAN1 gene is not found in the gnomAD database and changes the protein sequence starting at position 156 and interrupts the reading frame prematurely. This variant affects a moderately conserved nucleotide within a protein domain. ACMG criteria used for classification: PVS1_vstrg, PM2_supp.
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004784147 SCV005397473 likely pathogenic Developmental and epileptic encephalopathy, 5 2023-02-16 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (C>T) at coding position 466 of the SPTAN1 gene that converts an arginine residue to a premature stop sigl at codon 156. Because this premature termition sigl occurs in exon 4 of 57, this variant is predicted to generate a non-functiol allele through the expression of a truncated protein or the loss of SPTAN1 expression due to nonsense mediated decay. This is a novel variant that is absent from an online database of clinically annotated variants (ClinVar) and the gnomAD control population database (0 of approximately 250,000 alleles). To our knowledge, the variant has not been observed in an individual affected by a SPTAN1-related disorder in the published literature. Likewise, studies examining the functiol consequence of this variant have not been published. However, truncating variants are a known mechanism of disease for SPTAN1 (PMID: 34590414). Given this information, we consider this a likely pathogenic variant. ACMG Criteria: PM2, PVS1
GeneDx RCV005228023 SCV005870446 pathogenic not provided 2024-08-19 criteria provided, single submitter clinical testing Reported with a second SPTAN1 variant on the opposite allele (in trans) in a fetus with agenesis of the corpus callosum, severe left heart hypoplasia, and moderate facial asymmetry in a doctoral thesis (Alby-Averseng, 2015, https://theses.hal.science/tel-01627568); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Alby-Averseng_2015_Thesis)
Clinical Genetics Laboratory, Skane University Hospital Lund RCV005245549 SCV005894803 pathogenic Neurodevelopmental abnormality 2025-01-20 criteria provided, single submitter clinical testing Observed in a heterozygous state, at our lab, in a patient with matching phenotype. ACMG criteria used: PVS1, PS4_Moderate, PM2

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