Submissions for variant NM_183235.3(RAB27A):c.559C>T (p.Arg187Trp)

gnomAD frequency: 0.00016  dbSNP: rs144946000

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000823302	SCV000964156	uncertain significance	Griscelli syndrome type 2	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 187 of the RAB27A protein (p.Arg187Trp). This variant is present in population databases (rs144946000, gnomAD 0.05%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 29522846, 32638196). ClinVar contains an entry for this variant (Variation ID: 665092). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Illumina Laboratory Services, Illumina	RCV000823302	SCV001279919	uncertain significance	Griscelli syndrome type 2	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264024	SCV002542933	uncertain significance	Autoinflammatory syndrome	2019-05-01	criteria provided, single submitter	clinical testing