ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3689T>C (p.Ile1230Thr)

gnomAD frequency: 0.00001  dbSNP: rs777751518
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001956788 SCV002247631 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2023-03-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1230 of the SCN2A protein (p.Ile1230Thr). This variant is present in population databases (rs777751518, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1464059). 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) performed at Invitae indicates that this missense variant is expected to disrupt SCN2A 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.
GeneDx RCV002285523 SCV002576077 uncertain significance not provided 2022-09-20 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the extracellular loop between the S1 and S2 transmembrane segments of the third homologous domain; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004956010 SCV005500035 uncertain significance Inborn genetic diseases 2024-12-04 criteria provided, single submitter clinical testing The c.3689T>C (p.I1230T) alteration is located in exon 20 (coding exon 19) of the SCN2A gene. This alteration results from a T to C substitution at nucleotide position 3689, causing the isoleucine (I) at amino acid position 1230 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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