Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Royal Brompton Clinical Genetics And Genomics Laboratory, |
RCV000412514 | SCV000845653 | likely pathogenic | Sudden cardiac failure, infantile | 2017-09-14 | criteria provided, single submitter | clinical testing | The c.182C>T variant is present in 2/242228 individuals in the gnomAD control population in heterozygous form, and has previously been reported in compound heterozygosity with another likely pathogenic PPA2 variant in four siblings with sudden infantile cardiac failure, showing autosomal recessive inheritance (Guimier et al (2016) Am J Hum Genet 99(3):666-673). In silico analysis predicts a pathogenic effect on protein function and the affected amino acid is highly conserved. Functional studies indicated that this variant adversely affects protein function (Guimier et al (2016)). The variant was detected in compound heterozygosity with another pathogenic variant in the proband, and in heterozygous form in an unaffected parent. In view of this evidence, we have interpreted this variant as likely to be pathogenic when inherited with another (likely) pathogenic variant. The variant is likely to be benign when carried in isolation. |
| OMIM | RCV000412514 | SCV000490294 | pathogenic | Sudden cardiac failure, infantile | 2016-11-23 | no assertion criteria provided | literature only |