ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.3667A>G (p.Lys1223Glu)

gnomAD frequency: 0.00011  dbSNP: rs200269227
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000504153 SCV000596762 uncertain significance not specified 2016-04-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000794691 SCV000934115 uncertain significance Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2024-10-10 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1223 of the RELN protein (p.Lys1223Glu). This variant is present in population databases (rs200269227, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 436529). 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) indicates that this missense variant is not expected to disrupt RELN protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002481626 SCV002791266 uncertain significance Epilepsy, familial temporal lobe, 1; Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2021-08-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023401 SCV004939001 uncertain significance Inborn genetic diseases 2023-12-31 criteria provided, single submitter clinical testing The c.3667A>G (p.K1223E) alteration is located in exon 26 (coding exon 26) of the RELN gene. This alteration results from a A to G substitution at nucleotide position 3667, causing the lysine (K) at amino acid position 1223 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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