Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003665545 | SCV004376770 | pathogenic | not provided | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu116Valfs*66) 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). This variant is present in population databases (rs774522276, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CANT1-related conditions. For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV004594704 | SCV005086620 | pathogenic | Desbuquois dysplasia 1 | 2023-12-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with desbuquois dysplasia 1, (MIM#251450) and epiphyseal dysplasia, multiple, 7, (MIM#617719). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (2 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported as likely pathogenic and pathogenic, and observed in homozygous or compound heterozygous individuals with desbuquois dysplasia or features including short limbs, dysmorphic features and growth failure (ClinVar, PMID: 34602954, PMID: 22539336). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1207 - Parental origin of the variant is unresolved, as both parents are heterozygous (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |