ClinVar Miner

Submissions for variant NM_001130438.3(SPTAN1):c.6863C>T (p.Thr2288Met)

dbSNP: rs2132089093
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001893260 SCV002158428 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2024-04-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 2288 of the SPTAN1 protein (p.Thr2288Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1391770). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPTAN1 protein function. 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.
PreventionGenetics, part of Exact Sciences RCV004552080 SCV004121296 uncertain significance SPTAN1-related disorder 2022-11-07 criteria provided, single submitter clinical testing The SPTAN1 c.6863C>T variant is predicted to result in the amino acid substitution p.Thr2288Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Clinical Genomics Laboratory, Washington University in St. Louis RCV004555890 SCV005045001 uncertain significance Developmental and epileptic encephalopathy, 5 2023-12-10 criteria provided, single submitter clinical testing The SPTAN1 c.6863C>T (p.Thr2288Met) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on SPTAN1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
GeneDx RCV005057755 SCV005689952 uncertain significance not provided 2024-08-07 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge

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