Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001050283 | SCV001214382 | uncertain significance | Charcot-Marie-Tooth disease type 2B | 2022-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 161 of the RAB7A protein (p.Asn161Ser). 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. This variant disrupts the p.Asn161 amino acid residue in RAB7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15455439, 18272684, 23188822, 24498653, 26791407). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 846870). This variant has not been reported in the literature in individuals affected with RAB7A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). |