ClinVar Miner

Submissions for variant NM_001168338.1(PLG):c.112A>G (p.Lys38Glu) (rs73015965)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725124 SCV000334292 pathogenic not provided 2018-09-06 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000014551 SCV000538055 pathogenic Plasminogen deficiency, type I 2016-01-27 criteria provided, single submitter clinical testing The c.112A>G (p.Lys38Glu) missense variant in the PLG gene has been previously reported in numerous affected individuals with autosomal recessive Plasminogen Deficiency and has been shown to segregate with disease in affected family members (Schuster et al., 1999; Schuster et al., 2001). This variant has been observed in affected individuals in trans with multiple variants (Cys122Ter, Arg134Lys, Arg513His, Arg216His, and Leu128Pro) (Schuster et al., 1999; Schuster et al., 2001). Functional studies have shown this variant causes decreased serum plasminogen activity and decreased plasminogen antigen levels (Schuster et al., 1999; Schuster et al., 2001; Tefs et al., 2006). Case-control studies have found this variant to be significantly more prevalent in affected individuals relative to controls (Tefs et al., 2006). This c.112A>G has been reported in the three population databases at a frequency lower than the prevalence of the disease (Exome Sequencing Project [ESP] = 0.616%, 1000 Genomes = 1%, and ExAC = 0.496%). The PLG gene is the only gene in which mutations are known to cause Plasminogen Deficiency. Therefore, this collective evidence supports the classification of the c.112A>G (p.Lys38Glu) as a recessive Pathogenic variant for Plasminogen Deficiency.
Fulgent Genetics,Fulgent Genetics RCV000014551 SCV000893704 pathogenic Plasminogen deficiency, type I 2018-10-31 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000014551 SCV000899298 likely pathogenic Plasminogen deficiency, type I 2019-02-01 criteria provided, single submitter research
OMIM RCV000014551 SCV000034802 pathogenic Plasminogen deficiency, type I 2006-11-01 no assertion criteria provided literature only
Santos-Cortez Lab,University of Colorado School of Medicine RCV000999694 SCV000996503 benign Otitis media, susceptibility to 2019-07-26 no assertion criteria provided research
Reproductive Health Research and Development,BGI Genomics RCV000014551 SCV001142366 pathogenic Plasminogen deficiency, type I 2020-01-06 no assertion criteria provided curation NM_000301.3:c.112A>G in the PLG gene has an allele frequency of 0.005 in European (non-Finnish) subpopulation in the gnomAD database. This variant has been observed in affected individuals in trans with multiple variants (Cys122Ter, Arg134Lys, Arg513His, Arg216His, and Leu128Pro) (PMID: 10233898; 12850227). Functional studies have shown this variant causes decreased serum plasminogen activity and decreased plasminogen antigen levels (PMID: 16849641). Case-control studies have found this variant to be significantly more prevalent in affected individuals relative to controls (PMID: 16849641). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PM3_VeryStrong; PS3; PS4; PP4.

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