Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000024006 | SCV000914802 | likely pathogenic | Desbuquois dysplasia 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | The CANT1 c.228dupC (p.Trp77LeufsTer13) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Trp77LeufsTer13 has been reported in two studies and found in a total of three individuals affected with Desbuquois dysplasia, including one in a homozygous state and two in a compound heterozygous state (Furuichi et al. 2011; Laccone et al. 2011). The variant was absent from 200 control individuals and is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database in a region of good sequence coverage so the variant is presumed to be rare. Based on the potential impact of frameshift variants and the evidence, the p.Trp77LeufsTer13 variant is classified as likely pathogenic for Desbuquois dysplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001852562 | SCV002243043 | pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp77Leufs*13) in the CANT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CANT1 are known to be pathogenic (PMID: 19853239, 21037275, 22539336). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Desbuquois dysplasia (PMID: 21037275, 21654728). ClinVar contains an entry for this variant (Variation ID: 31014). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001852562 | SCV004031846 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | Frameshift 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: 21037275, 34602954, 20358610, 21654728, 31847883) |
| OMIM | RCV000024006 | SCV000045297 | pathogenic | Desbuquois dysplasia 1 | 2011-11-01 | no assertion criteria provided | literature only |