Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806710 | SCV002050801 | likely pathogenic | Long QT syndrome | 2021-12-06 | criteria provided, single submitter | clinical testing | Variant summary: CAV3 c.213G>A (p.Trp71X) results in a premature termination codon, located in exon 2 (i.e. in the last exon) that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein. The variant was absent in 251174 control chromosomes (gnomAD). A different variant resulting in the same nonsense change at the protein level, c.212G>A (p.Trp71X), has been reported in a homozygous patient who was affected with rippling muscle disease (RMD), however, the electrocardiogram and cardiac sonogram were normal for this patient (Ueyama_2007). Though RMD is usually transmitted in an autosomal-dominant manner, other loss-of-function variants in the CAV3 gene have also been reported in individuals affected with recessive RMD (e.g. PMID: 16730439, 21294223, 18487559). These data indicate that the variant maybe be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic for autosomal recessive RMD phenotype. |