Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002227677 | SCV002506750 | uncertain significance | Developmental and epileptic encephalopathy, 47 | 2021-05-14 | criteria provided, single submitter | clinical testing | The c.37A>G (p.Lys13Glu) variant identified in the FGF12 gene substitutes a well conserved Lysine for Glutamic Acid at amino acid 13/244 (exon 1/5). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms do not agree on the effect of this variant, as it is predicted both Damaging (SIFT; score:0.002) and Benign (REVEL; score:0.517) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Lys13 residue is within the Bipartite nuclear localization signal of FGF12 (UniProtKB:P61328). Given the lack of compelling evidence for its pathogenicity, the c.37A>G (p.Lys13Glu) variant identified in the FGF12 gene is reported as a Variant of Uncertain Significance. |