ClinVar Miner

Submissions for variant NM_198576.4(AGRN):c.3004G>C (p.Gly1002Arg)

dbSNP: rs757677789
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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 RCV001905528 SCV002155775 uncertain significance Congenital myasthenic syndrome 8 2022-03-18 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1002 of the AGRN protein (p.Gly1002Arg). 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001905528 SCV005061116 uncertain significance Congenital myasthenic syndrome 8 criteria provided, single submitter clinical testing The observed missense c.3004G>C (p.Gly1002Arg) variant in AGRN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly1002Arg variant is present with an allele frequency of 0.001% in the gnomAD exomes database. This variant has been submitted to the ClinVar database as Uncertain Significance. The amino acid Gly at position 1002 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence predicts no damaging effect on protein structure and function for this variant (Sift - tolerated; Mutation Taster - Polymorphism automatic). For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
Breakthrough Genomics, Breakthrough Genomics RCV004691457 SCV005186492 uncertain significance not provided criteria provided, single submitter not provided

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