Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000816445 | SCV000956955 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 192 of the STXBP2 protein (p.Arg192His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 27209435, 27781387, 30899265). ClinVar contains an entry for this variant (Variation ID: 659435). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Illumina Laboratory Services, |
RCV000816445 | SCV001288654 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2017-11-17 | 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. |
| Gene |
RCV001796249 | SCV002032460 | uncertain significance | not provided | 2021-06-01 | criteria provided, single submitter | clinical testing | Identified in multiple individuals with hemophagocytc lymphohistiocytsosis in published literature, but additional information, such as second variants and segregation, was not provided (Xu et al., 2017; Chen et al., 2016; Miao et al., 2019 ); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 32571462, 27781387, 30899265, 27209435) |