ClinVar Miner

Submissions for variant NM_198576.4(AGRN):c.4999G>A (p.Val1667Met)

gnomAD frequency: 0.00003  dbSNP: rs770750909
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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 RCV001698934 SCV004343614 uncertain significance Congenital myasthenic syndrome 8 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1667 of the AGRN protein (p.Val1667Met). This variant is present in population databases (rs770750909, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of AGRN-related conditions (PMID: 35670010). ClinVar contains an entry for this variant (Variation ID: 1284257). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx RCV004728784 SCV005331578 uncertain significance not provided 2024-01-09 criteria provided, single submitter clinical testing Reported in the published literature in a patient with congenital myasthenia who also harbors and additional missense variant in the AGRN gene (PMID: 35670010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35670010)
Department of Neurology, Xiangya Hospital Central South University RCV001698934 SCV001916962 pathogenic Congenital myasthenic syndrome 8 2021-09-22 no assertion criteria provided clinical testing

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