ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.4640G>A (p.Arg1547Gln)

gnomAD frequency: 0.00003  dbSNP: rs774277969
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815399 SCV000955850 uncertain significance Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2022-07-19 criteria provided, single submitter clinical testing 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 658551). This variant has not been reported in the literature in individuals affected with RELN-related conditions. This variant is present in population databases (rs774277969, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1547 of the RELN protein (p.Arg1547Gln).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003396429 SCV004121888 uncertain significance not specified 2023-10-19 criteria provided, single submitter clinical testing Variant summary: RELN c.4640G>A (p.Arg1547Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251316 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4640G>A in individuals affected with Epilepsy Familial Temporal Lobe 7 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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