Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002947899 | SCV003271564 | uncertain significance | Thrombophilia due to protein S deficiency, autosomal recessive | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 445 of the PROS1 protein (p.Arg445His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs375034896, ExAC 0.04%). This missense change has been observed in individual(s) with clinical features of PROS1-related conditions (PMID: 30669159). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |