Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001222124 | SCV001394208 | pathogenic | Griscelli syndrome type 2 | 2023-09-12 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAB27A-related conditions. This sequence change creates a premature translational stop signal (p.Pro126Glnfs*3) in the RAB27A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAB27A are known to be pathogenic (PMID: 10835631, 23160464). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 950420). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002562548 | SCV003630543 | pathogenic | Inborn genetic diseases | 2022-06-17 | criteria provided, single submitter | clinical testing | The c.377delC (p.P126Qfs*3) alteration, located in exon 5 (coding exon 4) of the RAB27A gene, consists of a deletion of one nucleotide at position 377, causing a translational frameshift with a predicted alternate stop codon after 3 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been detected in the homozygous state in an individual with Griscelli syndrome (Tengsujaritkul, 2022). It has also been detected in conjunction with another RAB27A alteration in an individual with primary hemophagocytic lymphohistiocytosis, which is part of the spectrum of Griscelli syndrome (Zhang, 2020). Based on the available evidence, this alteration is classified as pathogenic. |