ClinVar Miner

Submissions for variant NM_198576.4(AGRN):c.523A>G (p.Met175Val)

gnomAD frequency: 0.00020  dbSNP: rs575663792
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812415 SCV000952726 uncertain significance Congenital myasthenic syndrome 8 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 175 of the AGRN protein (p.Met175Val). This variant is present in population databases (rs575663792, gnomAD 0.08%). 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: 656091). 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 valine 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.
GeneDx RCV001766702 SCV001991568 uncertain significance not provided 2019-08-11 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002538118 SCV003727778 uncertain significance Inborn genetic diseases 2022-07-20 criteria provided, single submitter clinical testing The c.523A>G (p.M175V) alteration is located in exon 4 (coding exon 4) of the AGRN gene. This alteration results from a A to G substitution at nucleotide position 523, causing the methionine (M) at amino acid position 175 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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