ClinVar Miner

Submissions for variant NM_006949.4(STXBP2):c.568C>T (p.Arg190Cys)

gnomAD frequency: 0.00041  dbSNP: rs370053399
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477888 SCV000769113 likely benign Familial hemophagocytic lymphohistiocytosis 5 2024-01-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000658815 SCV000780611 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000658815 SCV000861500 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000477888 SCV000899004 uncertain significance Familial hemophagocytic lymphohistiocytosis 5 2021-03-30 criteria provided, single submitter clinical testing STXBP2 NM_006949 exon 7 p.Arg190Cys (c.568C>T): This variant has been reported in the literature in 1 individual with hemophagocytic lymphohistiocytosis as a double heterozygote (Zhang 2014 PMID:24916509). This variant is present in 0.2% (21/8488) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs370053399). This variant is present in ClinVar (Variation ID:404841). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Laboratory Services, Illumina RCV000477888 SCV001288653 uncertain significance Familial hemophagocytic lymphohistiocytosis 5 2017-05-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526685 SCV005039758 uncertain significance not specified 2024-03-19 criteria provided, single submitter clinical testing Variant summary: FANCC c.568C>T (p.Leu190Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251376 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.568C>T has been reported in the literature in individuals affected with Fanconi Anemia Group C. These report(s) do not provide unequivocal conclusions about association of the variant with Fanconi Anemia Group C. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Division of Human Genetics, Children's Hospital of Philadelphia RCV000477888 SCV000536933 uncertain significance Familial hemophagocytic lymphohistiocytosis 5 2016-05-28 no assertion criteria provided research
GeneReviews RCV000477888 SCV001976574 not provided Familial hemophagocytic lymphohistiocytosis 5 no assertion provided literature only Dominant-negative variant assoc w/fHLH in 1 infant [Benavides et al 2020]

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