Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001218865 | SCV001390770 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 3 | 2019-05-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 398 of the UNC13D protein (p.Ser398Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs747756030, ExAC 0.002%). This variant has been observed in an individual affected with hemophagocytic lymphohistiocytosis (PMID: 21248318). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
3billion | RCV001218865 | SCV002058394 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 3 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |