ClinVar Miner

Submissions for variant NM_198576.4(AGRN):c.2987C>A (p.Ala996Glu)

gnomAD frequency: 0.00057  dbSNP: rs148475305
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540503 SCV000653902 uncertain significance Congenital myasthenic syndrome 8 2022-10-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 996 of the AGRN protein (p.Ala996Glu). This variant is present in population databases (rs148475305, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 474111). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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