ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.5514G>C (p.Gln1838His) (rs547095921)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189240 SCV000242872 uncertain significance not provided 2015-10-14 criteria provided, single submitter clinical testing The Q1838H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1838H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a conserved position in the C-terminal cytoplasmic region of the SCN2A protein (Shi et al., 2012), and in silico analysis predicts this variant is probably damaging to the protein structure/function. The variant is found in EPILEPSY panel(s).
Invitae RCV001070208 SCV001235425 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-04-26 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1838 of the SCN2A protein (p.Gln1838His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs547095921, ExAC 0.02%). This variant has not been reported in the literature in individuals with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 207085). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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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