ClinVar Miner

Submissions for variant NM_006922.4(SCN3A):c.295A>G (p.Ile99Val)

gnomAD frequency: 0.00004  dbSNP: rs200538599
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178282 SCV000230334 uncertain significance not provided 2014-11-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000178282 SCV000963782 likely pathogenic not provided 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 99 of the SCN3A protein (p.Ile99Val). This variant is present in population databases (rs200538599, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of SCN3A-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 197285). Invitae Evidence 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 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 SCN3A protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV002517725 SCV003734851 uncertain significance Inborn genetic diseases 2022-11-03 criteria provided, single submitter clinical testing The c.295A>G (p.I99V) alteration is located in exon 4 (coding exon 2) of the SCN3A gene. This alteration results from a A to G substitution at nucleotide position 295, causing the isoleucine (I) at amino acid position 99 to be replaced by a valine (V). The in silico prediction for the p.I99V alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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