Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000687553 | SCV000815128 | uncertain significance | Bloom syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 364 of the BLM protein (p.Arg364Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 567460). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Natera, |
RCV000687553 | SCV002090007 | uncertain significance | Bloom syndrome | 2020-02-21 | no assertion criteria provided | clinical testing |