Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001985948 | SCV002263965 | uncertain significance | Developmental and epileptic encephalopathy, 25 | 2020-10-26 | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 SLC13A5-related conditions. This variant is present in population databases (rs530676026, ExAC 0.008%). This sequence change replaces arginine with glutamine at codon 123 of the SLC13A5 protein (p.Arg123Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant also falls at the last nucleotide of exon 3, which is part of the consensus splice site for this exon. |