ClinVar Miner

Submissions for variant NM_001130438.3(SPTAN1):c.6899_6907ACCAGCTGG[3] (p.2300_2302DQL[3]) (rs587784440)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147656 SCV000195105 pathogenic Early infantile epileptic encephalopathy 5 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000189556 SCV000243199 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing c.6908_6916dupACCAGCTGG: p.Asp2303_Leu2305dup in exon 53 in the SPTAN1 gene (NM_001130438.2). The normal sequence with the bases that are duplicated in braces is: CTGG{ACCAGCTGG}GCAT. The c.6908_6916dupACCAGCTGG variant in the SPTAN1 gene was reported previously as a de novo mutation in a child with West syndrome and hypomyelination (Nonoda et al., 2012). This duplication results in an in-frame duplication of three well-conserved amino acids in the last spectrin repeat, starting with codon Aspartic Acid 2303 and ending at codon Leucine 2305, denoted p.Asp2303_Leu2305dup. Previously reported pathogenic variants in SPTAN1 include in-frame deletions or duplications located within the last four spectrin repeats of the protein, which are essential for dimerization (Saitsu et al., 2010), and this variant is within the this region. The c.6908_6916dupACCAGCTGG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.6908_6916dupACCAGCTGG as a pathogenic variant.
Invitae RCV000696609 SCV000825175 uncertain significance Early infantile epileptic encephalopathy 2017-10-17 criteria provided, single submitter clinical testing This variant, c.6908_6916dupACCAGCTGG, results in the insertion of 3 amino acids to the SPTAN1 protein (p.Asp2303_Leu2305dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with West syndrome with progressive diffuse brain atrophy (PMID: 22656320). ClinVar contains an entry for this variant (Variation ID: 160028). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000718858 SCV000849722 pathogenic Seizures 2017-05-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Well-characterized mutation at same position,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000189556 SCV000862913 pathogenic not provided 2018-08-30 criteria provided, single submitter clinical testing
OMIM RCV000147656 SCV000223691 pathogenic Early infantile epileptic encephalopathy 5 2013-03-01 no assertion criteria provided literature only

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