ClinVar Miner

Submissions for variant NM_000301.5(PLG):c.1735G>A (p.Gly579Arg)

gnomAD frequency: 0.00027  dbSNP: rs138728014
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002493459 SCV002787323 uncertain significance Plasminogen deficiency, type I; Angioedema, hereditary, 4 2022-03-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002537721 SCV003267134 uncertain significance not provided 2025-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 579 of the PLG protein (p.Gly579Arg). This variant is present in population databases (rs138728014, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 988227). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PLG protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002537722 SCV003640235 uncertain significance Inborn genetic diseases 2022-10-25 criteria provided, single submitter clinical testing The c.1735G>A (p.G579R) alteration is located in exon 14 (coding exon 14) of the PLG gene. This alteration results from a G to A substitution at nucleotide position 1735, causing the glycine (G) at amino acid position 579 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics RCV002537721 SCV005189334 uncertain significance not provided criteria provided, single submitter not provided
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328254 SCV001449407 uncertain significance Atypical hemolytic-uremic syndrome 2018-08-27 no assertion criteria provided clinical testing This patient is heterozygous for a variant of uncertain significance (VOUS), c.1735G>A (p.Gly579Arg), in the PLG gene. To our knowledge, this variant has not been previously reported in the literature to be associated with disease. This variant has been reported in the ExAC database (http://exac.broadinstitute.org) with a low allele frequency of 0.026% (31/121370 alleles). In silico analysis (using Alamut Visual 2.8.1) using PolyPhen2, SIFT and Mutation Taster suggest that this variant is likely to be pathogenic. PLG variants have been reported in patients with aHUS and C3GN (Bu et al 2015 J Am Soc Nephrol 27:1245-53) with an autosomal dominant inheritance as well as in plasminogen deficiency and dysplasminogenemia (OMIM 173350) with an autosomal recessive inheritance.

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