Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000997886 | SCV001153641 | likely pathogenic | not provided | 2018-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000997886 | SCV001577866 | likely pathogenic | not provided | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 357 of the SMARCB1 protein (p.Thr357Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of Coffin-Siris syndrome (Invitae). In at least one individual the variant was observed to be de novo. 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 C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |