Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000499948 | SCV000597498 | uncertain significance | not specified | 2015-09-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000812896 | SCV000953226 | uncertain significance | Joubert syndrome 16 | 2018-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 25 of the TMEM138 protein (p.Asn25Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs775913576, ExAC 0.01%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TMEM138-related conditions. ClinVar contains an entry for this variant (Variation ID: 437008). |
Gene |
RCV001662500 | SCV001873023 | uncertain significance | not provided | 2021-09-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22282472) |