Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000354112 | SCV000329288 | pathogenic | not provided | 2016-08-04 | criteria provided, single submitter | clinical testing | The CHM gene encodes Rab escort protein 1, a RAB geranylgeranyl transferase subunit necessary for the postranslational modification and membrane targeting of Rab proteins (van den Hurk et al., 2003). Pathogenic variants in the CHM gene cause choroideremia, an X-linked form of retinal dystrophy characterized by retinal pigment epithelium and photoreceptor degeneration with eventual complete choroid atrophy and bare sclera (van den Hurk et al., 1997; Guo et al., 2015; Sanchez-Alcudia et al., 2016). Affected males have night blindness, tunnel vision, and may eventually become completely blind (van den Hurk et al., 2003). Rarely, female carriers may be affected, but typically have only mild cone dysfunction, mottled irregularity of the fundus, and yellowish flecks in the macula over time (Cremers et al., 1990, van den Hurk et al., 1997, Renner et al., 2009). |
Blueprint Genetics | RCV001075589 | SCV001241216 | likely pathogenic | Retinal dystrophy | 2019-01-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000354112 | SCV002237507 | pathogenic | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 279770). Disruption of this splice site has been observed in individual(s) with choroideremia (PMID: 21905166, 27247961). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the CHM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHM are known to be pathogenic (PMID: 9067750, 23811034). |
Gene |
RCV001775108 | SCV002012456 | not provided | Choroideremia | no assertion provided | literature only |