Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000190663 | SCV000244103 | pathogenic | Inborn genetic diseases | 2013-09-10 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000001019 | SCV000465592 | pathogenic | Leber congenital amaurosis 5 | 2017-04-27 | criteria provided, single submitter | clinical testing | The LCA5 c.835C>T (p.Gln279Ter) variant is a stop-gained variant that is described in four studies, in which it was found in a homozygous state in five patients with Leber congenital amaurosis (LCA) and in a compound heterozygous state in three patients with LCA (den Hollander et al. 2007; Jacobson et al. 2009; MacKay et al. 2013; Farwell et al. 2015). The variant was absent from 180 total controls but is reported at a frequency of 0.00035 in the European American population of the Exome Sequencing Project. Functional studies by Boldt et al. (2011) showed that the p.Gln279Ter variant resulted in a total loss of the protein interactions shown by wild type libercilin with the intraflagellar transport (IFT) machinery. IFT-dependent protein transport is an evolutionarily conserved basic mechanism found in all cilia. The variant also caused a loss of additional protein binding capabilities. Based on the collective evidence, the p.Gln279Ter variant is classified as pathogenic for Leber congenital amaurosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000812173 | SCV000952477 | pathogenic | not provided | 2019-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln279*) in the LCA5 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs121918165, ExAC 0.02%). This variant has been reported as homozygous or compound heterozygous in several individuals affected with Leber congenital amaurosis (PMID: 17546029, 23946133). ClinVar contains an entry for this variant (Variation ID: 968). Experimental studies have shown that this nonsense change abolishes interaction with intraflagellar transport components (PMID: 21606596). Loss-of-function variants in LCA5 are known to be pathogenic (PMID: 17546029, 23946133). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001073263 | SCV001238799 | pathogenic | Retinal dystrophy | 2018-09-26 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001019 | SCV000021169 | pathogenic | Leber congenital amaurosis 5 | 2007-07-01 | no assertion criteria provided | literature only | |
Gene |
RCV000001019 | SCV000087066 | pathologic | Leber congenital amaurosis 5 | 2013-05-02 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Sharon lab, |
RCV001003073 | SCV001161130 | pathogenic | Leber congenital amaurosis | 2019-06-23 | no assertion criteria provided | research | |
Laboratory of Genetics in Ophthalmology, |
RCV000001019 | SCV001433630 | pathogenic | Leber congenital amaurosis 5 | no assertion criteria provided | research | ||
Natera, |
RCV001003073 | SCV001453528 | pathogenic | Leber congenital amaurosis | 2020-09-16 | no assertion criteria provided | clinical testing |