Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520046 | SCV000619697 | uncertain significance | not provided | 2017-08-01 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the GOSR2 gene. The F87S variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.The F87S variant is not observed at a significant frequency in large population cohorts (Lek et al.,2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F87S variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs at aposition that is conserved across species. In silico analysis predicts this variant is probably damaging tothe protein structure/function. Therefore, based on the currently available information, it is unclearwhether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001224909 | SCV001397136 | uncertain significance | Progressive myoclonic epilepsy | 2023-08-10 | criteria provided, single submitter | clinical testing | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 87 of the GOSR2 protein (p.Phe87Ser). This variant is present in population databases (rs374912150, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with GOSR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451051). 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. |