Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002633 | SCV001160616 | uncertain significance | Retinitis pigmentosa 43 | 2019-06-19 | criteria provided, single submitter | clinical testing | The PDE6A c.2369G>A; p.Arg790His variant (rs375516599), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the general population with an allele frequency of 0.01% (32/282858 alleles) in the Genome Aggregation Database. The amino acid at this position is highly conserved and computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of this variant is uncertain at this time. |
Labcorp Genetics |
RCV001860517 | SCV002196037 | uncertain significance | not provided | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 790 of the PDE6A protein (p.Arg790His). This variant is present in population databases (rs375516599, gnomAD 0.09%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 33946315). ClinVar contains an entry for this variant (Variation ID: 812056). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDE6A protein function. 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. |