ClinVar Miner

Submissions for variant NM_001130438.3(SPTAN1):c.4133T>C (p.Leu1378Pro)

gnomAD frequency: 0.00001  dbSNP: rs776728710
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559068 SCV000633776 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2017-02-25 criteria provided, single submitter clinical testing In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs776728710, ExAC 0.001%) but has not been reported in the literature in individuals with an SPTAN1-related disease. This sequence change replaces leucine with proline at codon 1378 of the SPTAN1 protein (p.Leu1378Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
Baylor Genetics RCV001332875 SCV001525314 uncertain significance Developmental and epileptic encephalopathy, 5 2020-03-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001755822 SCV001995453 uncertain significance not provided 2019-12-16 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV001332875 SCV002056759 uncertain significance Developmental and epileptic encephalopathy, 5 2021-07-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002330853 SCV002629341 uncertain significance Inborn genetic diseases 2022-09-22 criteria provided, single submitter clinical testing The c.4133T>C (p.L1378P) alteration is located in exon 32 (coding exon 31) of the SPTAN1 gene. This alteration results from a T to C substitution at nucleotide position 4133, causing the leucine (L) at amino acid position 1378 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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