ClinVar Miner

Submissions for variant NM_006922.4(SCN3A):c.1060A>C (p.Lys354Gln)

dbSNP: rs1553535457
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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 RCV001299125 SCV001488204 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 354 of the SCN3A protein (p.Lys354Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with an SCN3A-related condition (PMID: 18242854). ClinVar contains an entry for this variant (Variation ID: 440968). 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 not expected to disrupt SCN3A protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects SCN3A function (PMID: 18242854, 20420834, 24157691). 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.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001299125 SCV004244579 uncertain significance not provided 2023-10-09 criteria provided, single submitter clinical testing PM2, BS2
Ambry Genetics RCV004965521 SCV005500064 uncertain significance Inborn genetic diseases 2024-07-25 criteria provided, single submitter clinical testing The c.1060A>C (p.K354Q) alteration is located in exon 10 (coding exon 8) of the SCN3A gene. This alteration results from a A to C substitution at nucleotide position 1060, causing the lysine (K) at amino acid position 354 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen RCV000509281 SCV000606977 not provided SCN3A-related disorder no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Channelopathy-Associated Epilepsy Research Center RCV003992309 SCV004809311 not provided Early infantile epileptic encephalopathy with suppression bursts no assertion provided literature only

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