ClinVar Miner

Submissions for variant NM_183235.3(RAB27A):c.340A>G (p.Ile114Val)

gnomAD frequency: 0.00002  dbSNP: rs1218762595
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001926331 SCV002205987 uncertain significance Griscelli syndrome type 2 2022-08-09 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.007%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 not expected to disrupt RAB27A protein function. ClinVar contains an entry for this variant (Variation ID: 1422906). This variant has not been reported in the literature in individuals affected with RAB27A-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 114 of the RAB27A protein (p.Ile114Val).
Neuberg Centre For Genomic Medicine, NCGM RCV001926331 SCV004047941 uncertain significance Griscelli syndrome type 2 criteria provided, single submitter clinical testing The missense variant c.340A>G (p.Ile114Val) in RAB27A has been submitted to ClinVar as a Variant of Uncertain Significance (VUS). This p.Ile114Val variant has allele frequency of 0.0003980% in the gnomAD and novel (not in any individuals) in 1000 genome database. The amino acid Ile at position 114 is changed to a Val changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ile114Val in RAB27A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).

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