ClinVar Miner

Submissions for variant NM_000301.5(PLG):c.988A>G (p.Lys330Glu)

gnomAD frequency: 0.00001  dbSNP: rs889957249
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001862090 SCV002228205 pathogenic not provided 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 330 of the PLG protein (p.Lys330Glu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with hereditary angioedema (PMID: 28795768, 29548426). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1100A>G (p.Lys311Glu). ClinVar contains an entry for this variant (Variation ID: 590291). 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%. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001507288 SCV002762862 pathogenic Angioedema, hereditary, 4 2022-12-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003420282 SCV004114206 pathogenic PLG-related disorder 2023-04-30 criteria provided, single submitter clinical testing The PLG c.988A>G variant is predicted to result in the amino acid substitution p.Lys330Glu. This variant, also known as K330E, has been reported in many individuals with hereditary angioedema with normal C1 inhibitor (HAEnCI) (Bork K et al 2017. PubMed ID: 28795768; Dewald et al 2018. PubMed ID: 29548426; Belbézier A et al 2018. PubMed ID: 29952006; Yakushiji H et al 2018. PubMed ID: 29987869; Bork K et al 2020. PubMed ID: 32065705; Parsopoulou F et al 2020. PubMed ID: 32181895). This variant was observed to segregate with disease in at least a few families while showing incomplete penetrance. Functional studies revealed that this variant leads to altered PLG glycosylation and increased sensitivity to plasminogen activators (Dewald et al 2018. PubMed ID: 29548426; Parsopoulou F et al 2020. PubMed ID: 32181895) This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-161139762-A-G). This variant is interpreted as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005034336 SCV005668200 pathogenic Plasminogen deficiency, type I; Angioedema, hereditary, 4 2024-01-29 criteria provided, single submitter clinical testing
ITMI RCV000768407 SCV000844988 pathogenic Hereditary angioneurotic edema 2018-08-06 no assertion criteria provided research
OMIM RCV001507288 SCV001712260 pathogenic Angioedema, hereditary, 4 2025-01-16 no assertion criteria provided literature only

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