Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760516 | SCV000890407 | pathogenic | not provided | 2022-12-15 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28837078, 24680887, 29057815, 30081015, 31556760, 31456290, 34662339, 36317312, 32052671) |
Invitae | RCV000760516 | SCV001208150 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg76*) in the KIZ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIZ are known to be pathogenic (PMID: 24680887, 29057815). This variant is present in population databases (rs202210819, gnomAD 0.7%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 24680887, 28837078, 29057815, 31556760, 32052671; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 128241). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001073648 | SCV001239199 | pathogenic | Retinal dystrophy | 2019-07-27 | criteria provided, single submitter | clinical testing | |
Ocular Genomics Institute, |
RCV000116208 | SCV001573450 | pathogenic | Retinitis pigmentosa 69 | 2021-04-08 | criteria provided, single submitter | research | The PLK1S1 c.226C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM3, PP4. Based on this evidence we have classified this variant as Pathogenic. |
Fulgent Genetics, |
RCV000116208 | SCV002813808 | pathogenic | Retinitis pigmentosa 69 | 2021-10-19 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000116208 | SCV003818832 | pathogenic | Retinitis pigmentosa 69 | 2022-12-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003390800 | SCV004120586 | pathogenic | KIZ-related condition | 2023-08-14 | criteria provided, single submitter | clinical testing | The KIZ c.226C>T variant is predicted to result in premature protein termination (p.Arg76*). This variant has been reported in the homozygous and compound heterozygous states in individuals with rod-cone dystrophy (El Shamieh et al. 2014. PubMed ID: 24680887; El Shamieh et al. 2017. PubMed ID: 29057815; Gustafson et al. 2017. PubMed ID: 28837078; Table S2 in Sharon et al. 2019. PubMed ID: 31456290). This variant is reported in 0.63% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-21117104-C-T). Nonsense variants in KIZ are expected to be pathogenic. Given the evidence, we interpret c.226C>T (p.Arg76*) as pathogenic. |
OMIM | RCV000116208 | SCV000150117 | pathogenic | Retinitis pigmentosa 69 | 2014-04-03 | no assertion criteria provided | literature only | |
Reproductive Health Research and Development, |
RCV000116208 | SCV001142495 | pathogenic | Retinitis pigmentosa 69 | 2020-01-06 | no assertion criteria provided | curation | NM_018474.5:c.226C>T in the KIZ gene has an allele frequency of 0.006 in Ashkenazi Jewish subpopulation in the gnomAD database. The p.Arg76* (NM_018474.5:c.226C>T) variant in the KIZ gene has been reported in retinitis pigmentosa patients with a homozygous mutation (PMID: 24680887; 2905781). This variant is presented in the biological transcript and located at the 3/13 exon, therefore, it is predicted to lead nonsense-mediated mRNA decay. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM3; PP4. |
Sharon lab, |
RCV001003070 | SCV001161127 | pathogenic | Retinitis pigmentosa | 2019-06-23 | no assertion criteria provided | research | |
Broad Center for Mendelian Genomics, |
RCV000116208 | SCV001445951 | pathogenic | Retinitis pigmentosa 69 | 2023-06-05 | no assertion criteria provided | curation | The homozygous p.Arg76Ter variant in KIZ was identified by our study in 2 siblings with retinitis pigmentosa. The variant has been reported in 9 individuals with retinitis pigmentosa (PMID: 28837078, 24680887, 29057815, 32052671, 31556760), segregated with disease in 2 affected relatives from 2 families (PMID: 28837078), and has been identified in 0.63% (61/9658) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs202210819). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID: 128241) as pathogenic by GeneDx, OMIM, Sharon lab, Hadassah-Hebrew University Medical Center, and Reproductive Health Research and Development, BGI Genomics. Of the 9 affected individuals, all were homozygotes, which increases the likelihood that the p.Arg76Ter variant is pathogenic (PMID: 28837078, 24680887, 29057815, 32052671, 31556760). This nonsense variant leads to a premature termination codon at position 76, which is predicted to lead to a truncated or absent protein. Loss of function of the KIZ gene is an established disease mechanism in autosomal recessive retinitis pigmentosa. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive retinitis pigmentosa. ACMG/AMP Criteria applied: PVS1, PM3, PP1 (Richards 2015). |