ClinVar Miner

Submissions for variant NM_005097.4(LGI1):c.1318G>A (p.Val440Met)

gnomAD frequency: 0.00003  dbSNP: rs144400448
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002232891 SCV000817650 uncertain significance Autosomal dominant epilepsy with auditory features 2022-10-17 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. 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 LGI1 protein function. ClinVar contains an entry for this variant (Variation ID: 569365). This variant has not been reported in the literature in individuals affected with LGI1-related conditions. This variant is present in population databases (rs144400448, gnomAD 0.007%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 440 of the LGI1 protein (p.Val440Met).
Ambry Genetics RCV002544859 SCV003677631 uncertain significance Inborn genetic diseases 2021-12-27 criteria provided, single submitter clinical testing The c.1318G>A (p.V440M) alteration is located in exon 8 (coding exon 8) of the LGI1 gene. This alteration results from a G to A substitution at nucleotide position 1318, causing the valine (V) at amino acid position 440 to be replaced by a methionine (M). Based on data from gnomAD, the A allele has an overall frequency of 0.0016% (4/251136) total alleles studied. The highest observed frequency was 0.006% (1/16256) of African alleles. This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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