Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001366985 | SCV001563313 | uncertain significance | Pierson syndrome; LAMB2-related infantile-onset nephrotic syndrome | 2020-01-24 | criteria provided, single submitter | clinical testing | 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with LAMB2-related conditions. This variant is present in population databases (rs567153631, ExAC 0.01%). This sequence change replaces glycine with serine at codon 518 of the LAMB2 protein (p.Gly518Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |