Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001307584 | SCV001497002 | uncertain significance | Costello syndrome | 2020-01-08 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with HRAS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 90 of the HRAS protein (p.Phe90Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |
Gene |
RCV004779049 | SCV005392539 | uncertain significance | not provided | 2024-05-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |