Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803682 | SCV000943564 | uncertain significance | Fanconi anemia | 2018-12-06 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FANCM-related conditions. This variant is present in population databases (rs768667842, ExAC 0.002%). This sequence change replaces threonine with lysine at codon 1249 of the FANCM protein (p.Thr1249Lys). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and lysine. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478504 | SCV004218782 | uncertain significance | not provided | 2023-02-03 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000041 (1/244790 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |