Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002231250 | SCV000629354 | uncertain significance | Long QT syndrome 1 | 2018-08-07 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CALM2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 3 of the CALM2 gene. It does not directly change the encoded amino acid sequence of the CALM2 protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000786283 | SCV000925041 | uncertain significance | not provided | 2017-08-15 | no assertion criteria provided | provider interpretation | CALM2, Intron 3, c.179-8C>G (Intronic), heterozygous, Uncertain Significance Given the lack of case data, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). CALM2 variants have been implicated in a long QT/CPVT-like phenotype (Boczek et al 2016). To date the reported cases have been quite severe with early childhood onset. Given the way some of these cases were ascertained (from large unexplained LQTS cohorts) it is unlikely that this greater severity is attributable primarily to ascertainment bias. Per the lab report this variant has not been reported in association with disease. Per the lab report "Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variantdisrupt the consensus splice site, but this prediction has not been confirmed by published studies." There is no variation at this nucleotide listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The average coverage at that site in gnomAD is >30x. |