Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002644351 | SCV003521141 | likely pathogenic | Leber congenital amaurosis 13 | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 187 of the RDH12 protein (p.Asp187Asn). This variant is present in population databases (rs115356583, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal recessive retinal dystrophy (PMID: 34001834). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2201291). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RDH12 protein function with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002644352 | SCV003642901 | uncertain significance | Inborn genetic diseases | 2022-07-26 | criteria provided, single submitter | clinical testing | The c.559G>A (p.D187N) alteration is located in exon 7 (coding exon 5) of the RDH12 gene. This alteration results from a G to A substitution at nucleotide position 559, causing the aspartic acid (D) at amino acid position 187 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |