ClinVar Miner

Submissions for variant NM_032607.3(CREB3L3):c.718G>A (p.Glu240Lys)

gnomAD frequency: 0.00002  dbSNP: rs778428363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GBinsight Genetic Testing by GB HealthWatch, Genben Lifesciences Corporation RCV001175123 SCV001322141 likely pathogenic Hypertriglyceridemia 1 2020-05-27 criteria provided, single submitter clinical testing Proband referred for clinical genetic testing presented with severe hypertriglyceridemia, low HDL-cholesterol and type 2 diabetes. Clinical genetic testing identified heterozygosity for the p.Glu240Lys (NM_032607.3:c.718G>A) genetic variant in the the germline. The pathogenicity of this variant is supported by several publications that have demonstrated that this variant is a loss-of-function and is a cause of severe hypertriglyceridemia.
AiLife Diagnostics, AiLife Diagnostics RCV002223991 SCV002501996 likely pathogenic not provided 2021-12-26 criteria provided, single submitter clinical testing
Invitae RCV002223991 SCV004297981 uncertain significance not provided 2023-05-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 240 of the CREB3L3 protein (p.Glu240Lys). 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. Experimental studies have shown that this missense change affects CREB3L3 function (PMID: 21666694). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CREB3L3 protein function. ClinVar contains an entry for this variant (Variation ID: 917849). This missense change has been observed in individual(s) with clinical features of hypertriglyceridemia (PMID: 21666694, 31619059, 32041611). This variant is present in population databases (rs778428363, gnomAD 0.01%).

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