ClinVar Miner

Submissions for variant NM_003476.5(CSRP3):c.364C>T (p.Arg122Ter) (rs902082118)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769302 SCV000900680 likely pathogenic Cardiomyopathy 2015-10-15 criteria provided, single submitter clinical testing
GeneDx 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.

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