Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000006240 | SCV000915751 | uncertain significance | Cone-rod dystrophy | 2018-10-24 | criteria provided, single submitter | clinical testing | The UNC119 c.169A>T (p.Lys57Ter) variant is a stop-gained variant that has been reported in one patient with late-onset cone-rod dystrophy (CRD) in a heterozygous state (Kobayashi et al. 2000). The variant was also found in the patient's 36-year-old daughter who shared a history of seeing bright flashes with her mother but did not as yet have a clinical diagnosis of CRD (Kobayashi et al. 2000). The p.Lys57Ter variant was absent from 100 controls but is reported at a frequency of 0.000378 in the European (Finnish) population of the Genome Aggregation Database. Functional studies in transgenic mice showed age-dependent fundus lesions compared with controls. In addition, electroretinogram analysis showed significant reduction in b-wave in transgenic mice older than one year compared to controls, light microscopy analysis showed changes to the retina, and electron microscopy showed changes consistent with retinal degeneration affecting the photoreceptor ribbon synapses (Kobayashi et al. 2000). Due to the potential impact of stop-gained variants and the evidence from the literature, the p.Lys57Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for cone-rod dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001241145 | SCV001414140 | uncertain significance | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys57*) in the UNC119 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in UNC119 cause disease. This variant is present in population databases (rs267607166, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with cone-rod dystrophy (PMID: 11006213). ClinVar contains an entry for this variant (Variation ID: 5882). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects UNC119 function (PMID: 11006213). 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. |
| OMIM | RCV003223390 | SCV000026422 | pathogenic | Cone-rod dystrophy 24 | 2000-10-01 | no assertion criteria provided | literature only |