Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000989169 | SCV001139389 | likely pathogenic | Leber congenital amaurosis 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001869358 | SCV002181577 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2022-08-01 | 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. Variants that disrupt 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 803001). This missense change has been observed in individual(s) with leber congenital amaurosis (PMID: 32865313). This variant is present in population databases (rs758239674, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 267 of the RPGRIP1 protein (p.Arg267Gln). This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon. |