ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3130G>T (p.Asp1044Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1197983141
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002318351 SCV000851754 uncertain significance Inborn genetic diseases 2017-05-31 criteria provided, single submitter clinical testing The p.D1044Y variant (also known as c.3130G>T), located in coding exon 16 of the SCN2A gene, results from a G to T substitution at nucleotide position 3130. The aspartic acid at codon 1044 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002534986 SCV003468487 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-05-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1044 of the SCN2A protein (p.Asp1044Tyr). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 590172). 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 with a positive predictive value of 95%. 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.

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