Description
Testing was performed by Invitae. Given the lack of case data and presence in population databases, 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"). The variant has been seen in at least 1 unrelated cases of ARVC (not including this patient's family). There have been no reports of this variant in cases of LVNC or left ventricular systolic dysfunction. The case data is weak. Fressart et al. (2010) report this variant in one of their index patients with ARVC. Patients were recruited in France and Switzerland. They classify it as a variant of uncertain significance but note that it had previously been reported as a mutation in Yu et al. (2008). However, it isn't completely clear that these are referring to the same variant. Yu et al. reports the DSP variant as c.7516G>A (p.Arg2339Gln) in one individual who did not meet criteria for ARVC, but who did have sustained VT, dilation of the RV and non-specific dysfunction of the RV. The transcript used in this paper is reported as the same transcript listed above. This is not the same c. or p. nomenclature. It seems likely that these are not, in fact, the same variant. In silico prediction models to not agree on the effect of this variant. There variant has been seen in 11 of 141,023 individuals 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 variant was specifically in 9 of 63,156 European individuals (MAF=0.007%) and 2 of 15,444 South Asian individuals (MAF=0.006%). Phenotypic information on these individuals is not publicly available.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |