Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001380267 | SCV001578265 | pathogenic | not provided | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 226 of the CANT1 protein (p.Val226Met). This variant is present in population databases (rs377546036, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive Desbuquois dysplasia ("Kim-variant") or multiple epiphyseal dysplasia (PMID: 21037275, 28742282). ClinVar contains an entry for this variant (Variation ID: 31018). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CANT1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects CANT1 function (PMID: 21037275). For these reasons, this variant has been classified as Pathogenic. |
| Mendelics | RCV000024010 | SCV002518636 | pathogenic | Desbuquois dysplasia 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001380267 | SCV004025733 | likely pathogenic | not provided | 2024-07-25 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with loss of enzymatic function (PMID: 21037275); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21412251, 30949876, 28742282, 21037275, Asif Mirza2023[Article]) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000024010 | SCV004804085 | pathogenic | Desbuquois dysplasia 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | Variant summary: CANT1 c.676G>A (p.Val226Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251052 control chromosomes (gnomAD). c.676G>A has been reported in the literature in multiple individuals affected with Desbuquois dysplasia or Multiple Epiphyseal Dysplasia (Furuichi_2011, Balasubramanian_2017). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in a substantial reduction of normal nucleotidase activity (Furuichi_2011). The following publications have been ascertained in the context of this evaluation (PMID: 21037275, 28742282). ClinVar contains an entry for this variant (Variation ID: 31018). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000024010 | SCV000045301 | pathogenic | Desbuquois dysplasia 1 | 2011-05-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000509573 | SCV000607726 | pathogenic | Epiphyseal dysplasia, multiple, 7 | 2011-05-01 | no assertion criteria provided | literature only |