ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.2566A>G (p.Ile856Val)

gnomAD frequency: 0.00002  dbSNP: rs371309082
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001233050 SCV001405628 uncertain significance Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2024-01-04 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 856 of the RELN protein (p.Ile856Val). This variant is present in population databases (rs371309082, gnomAD 0.003%). 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: 959663). 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 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.
Ambry Genetics RCV003166429 SCV003910314 uncertain significance Inborn genetic diseases 2023-03-06 criteria provided, single submitter clinical testing The c.2566A>G (p.I856V) alteration is located in exon 20 (coding exon 20) of the RELN gene. This alteration results from a A to G substitution at nucleotide position 2566, causing the isoleucine (I) at amino acid position 856 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003433088 SCV004155694 likely benign not provided 2023-10-01 criteria provided, single submitter clinical testing RELN: BP4

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