Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001931453 | SCV002203530 | uncertain significance | Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 | 2021-07-21 | 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. 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 tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with RELN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 1166 of the RELN protein (p.His1166Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Ambry Genetics | RCV004041944 | SCV004939000 | uncertain significance | Inborn genetic diseases | 2023-10-17 | criteria provided, single submitter | clinical testing | The c.3496C>T (p.H1166Y) alteration is located in exon 25 (coding exon 25) of the RELN gene. This alteration results from a C to T substitution at nucleotide position 3496, causing the histidine (H) at amino acid position 1166 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |