Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000653020 | SCV000774894 | uncertain significance | Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 | 2020-02-21 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RELN-related disease. This variant is present in population databases (rs754745320, ExAC 0.004%). This sequence change replaces aspartic acid with glycine at codon 2171 of the RELN protein (p.Asp2171Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |
| Ambry Genetics | RCV002534192 | SCV003604220 | uncertain significance | Inborn genetic diseases | 2022-01-27 | criteria provided, single submitter | clinical testing | The c.6512A>G (p.D2171G) alteration is located in exon 42 (coding exon 42) of the RELN gene. This alteration results from a A to G substitution at nucleotide position 6512, causing the aspartic acid (D) at amino acid position 2171 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |