Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003058475 | SCV003442949 | likely pathogenic | Griscelli syndrome type 2 | 2022-11-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies have shown that this missense change affects RAB27A function (PMID: 33362801). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAB27A protein function. This missense change has been observed in individuals with Griscelli syndrome type 2 (PMID: 28936583, 33362801). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 143 of the RAB27A protein (p.Val143Ala). |