Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001207756 | SCV001379122 | pathogenic | not provided | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 of the CNGB1 gene. It does not directly change the encoded amino acid sequence of the CNGB1 protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individuals with retinitis pigmentosa (PMID: 25324289; Invitae). ClinVar contains an entry for this variant (Variation ID: 143124). 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. For these reasons, this variant has been classified as Pathogenic. |
3billion | RCV002250572 | SCV002521880 | pathogenic | Retinitis pigmentosa 45 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.005%). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.90). The variant has been observed in multiple (>3) similarly affected unrelated individuals (3billion dataset, ClinVar ID: VCV000143124). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 33847019, 33946315). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Fulgent Genetics, |
RCV002250572 | SCV002797076 | likely pathogenic | Retinitis pigmentosa 45 | 2022-03-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001207756 | SCV003935447 | likely pathogenic | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Identified in individuals in the published literature with childhood onset night blindness who also harbored a second variant in CNGB1, although the phase of these variants was not confirmed (Nassisi et al., 2021); This variant is associated with the following publications: (PMID: 31054281, 33946315, 33847019, 25324289) |
Department of Ophthalmology and Visual Sciences Kyoto University | RCV000132646 | SCV000172597 | probable-pathogenic | Retinitis pigmentosa | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |