ClinVar Miner

Submissions for variant NM_018474.6(KIZ):c.119_122del (p.Lys40fs)

gnomAD frequency: 0.00008  dbSNP: rs587777377
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073516 SCV001239062 pathogenic Retinal dystrophy 2019-04-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001385861 SCV001585861 pathogenic not provided 2024-02-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys40Ilefs*14) 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 (rs587777377, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 24680887). 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: 128243). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017401 SCV004848621 pathogenic Retinitis pigmentosa 2022-04-12 criteria provided, single submitter clinical testing The p.Lys40IlefsX14 variant in KIZ has been reported in 7 individuals with retinitis pigmentosa, including three homozygotes and two compound heterozygotes with a second pathogenic KIZ variant (Lin 2020 PMID: 32052671, El Shamieh 2014 PMID: 24680887, Blueprint Genetics data, Invitae data). It has also been identified in 0.009% (7/75782) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 40 and leads to a premature termination codon 14 amino acids downstream. Loss of function of the KIZ gene is associated with autosomal recessive retinitis pigmentosa. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive retinitis pigmentosa. ACMG/AMP criteria applied: PM3_Strong, PVS1_Strong.
OMIM RCV000116210 SCV000150119 pathogenic Retinitis pigmentosa 69 2014-04-03 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.