Submissions for variant NM_183235.3(RAB27A):c.260C>T (p.Ala87Val)

dbSNP: rs201697259

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002050784	SCV002112299	likely pathogenic	Griscelli syndrome type 2	2020-12-02	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.Ala87 amino acid residue in RAB27A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16278825, 25544030, 26880764). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 variant has not been reported in the literature in individuals with RAB27A-related conditions. This variant is present in population databases (rs201697259, ExAC 0.002%). This sequence change replaces alanine with valine at codon 87 of the RAB27A protein (p.Ala87Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264399	SCV002542920	uncertain significance	Autoinflammatory syndrome	2018-12-01	criteria provided, single submitter	clinical testing