Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001341081 | SCV001534926 | uncertain significance | Thrombophilia due to protein S deficiency, autosomal recessive | 2021-06-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of protein S deficiency (Invitae). This variant is present in population databases (rs528604865, ExAC 0.06%). This sequence change replaces glutamic acid with valine at codon 576 of the PROS1 protein (p.Glu576Val). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and valine. |