Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413421 | SCV000490928 | likely pathogenic | not provided | 2015-04-02 | criteria provided, single submitter | clinical testing | The R122X variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The R122Xvariant was not observed in approximately 6,500 individuals of European and African American ancestry inthe NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.R122X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. In vivo studies have shown that CSRP3 (MLP) null mice develop dilatedcardiomyopathy with hypertrophy and heart failure due to a disrupted cardiomyocyte architecture (Arberet al., 1997). Further, myocardial biopsies of a patient with HCM harboring a heterozygous CSRP3missense variant showed myocyte disarray and a significantly reduced level of MPL protein, suggestingthat cardiomyopathy may stem from CSRP3 haploinsufficiency (Geier et al., 2008). Nevertheless, the vastmajority of mutations in the CSRP3 gene reported to date are missense changes (Stenson P et al., 2014).Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is abenign variant cannot be excluded. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769302 | SCV000900680 | likely pathogenic | Cardiomyopathy | 2015-10-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001861413 | SCV002195572 | pathogenic | Hypertrophic cardiomyopathy 12; Dilated cardiomyopathy 1M | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg122*) in the CSRP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSRP3 are known to be pathogenic (PMID: 12642359, 14567970, 16352453, 20087448, 34558151). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 31919335, 34558151). ClinVar contains an entry for this variant (Variation ID: 372584). For these reasons, this variant has been classified as Pathogenic. |
Ai |
RCV000413421 | SCV002502304 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing |