ClinVar Miner

Submissions for variant NM_003764.4(STX11):c.616G>A (p.Glu206Lys) (rs145347140)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenomeConnect, ClinGen RCV000509480 SCV000607347 not provided Familial hemophagocytic lymphohistiocytosis no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Illumina Clinical Services Laboratory,Illumina RCV000779494 SCV000916127 uncertain significance Hemophagocytic lymphohistiocytosis, familial, 4 2017-08-30 criteria provided, single submitter clinical testing The STX11 c.616G>A (p.Glu206Lys) missense variant has been reported in one study in a compound heterozygous state in one individual who presented with familial hemophagocytic lymphohistiocytosis at age five years (Marsh et al. 2010). The p.Glu206Lys variant was absent from 50 controls but is reported at a frequency of 0.00336 in the Other population of the Exome Aggregation Consortium. In vitro experiments using peripheral blood mononuclear cells from the compound heterozygous patient demonstrated a detectable mutated syntaxin 11 protein, but the NK cell degranulation and cytotoxicity activity was preserved (Marsh et al. 2010). Based on the limited evidence, the Glu206Lys variant is classified as a variant of unknown significance but suspicious for pathogenicity for familial hemophagocytic lymphohistiocytosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000779494 SCV000949820 uncertain significance Hemophagocytic lymphohistiocytosis, familial, 4 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 206 of the STX11 protein (p.Glu206Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs145347140, ExAC 0.2%). This variant has been observed in an individual affected with hemophagocytic lymphohistiocytosis (PMID: 20486178). ClinVar contains an entry for this variant (Variation ID: 403500). Experimental studies have shown that patient-derived cells harboring this p.Glu206Lys variant and a p.Glu36Gln variant display normal NK cell cytotoxicity (PMID: 20486178). However, the effect of each missense variant alone was not assessed and therefore the clinical impact of these findings is uncertain. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000454862 SCV000540472 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: seen in MedSeq case

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