Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000712671 | SCV000843190 | uncertain significance | not provided | 2018-06-25 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002493266 | SCV002799688 | uncertain significance | Polycystic kidney disease, adult type | 2022-04-02 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003403645 | SCV004104113 | uncertain significance | PKD1-related condition | 2023-04-28 | criteria provided, single submitter | clinical testing | The PKD1 c.9454C>T variant is predicted to result in the amino acid substitution p.Arg3152Trp. This variant was reported in an individual with ciliopathy; the individual also carried a truncating variant in PKD1 (Table 3: patient #52, Vaisitti et al. 2020. PubMed ID: 33226606). This variant is reported in 0.0040% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2150511-G-A). Of note, we have previously found this variant in the heterozygous state with a definitely pathogenic PKD1 variant in two newborns and one fetus with PKD at PreventionGenetics (internal data). Therefore, this variant is highly suspected to be a hypomorphic allele. By itself, it may cause no disease or only relatively mild disease. However, in combination with other pathogenic variants in relevant genes, this type of hypomorphic allele may contribute to disease severity. Therefore, the pathogenicity of the c.9454C>T (p.Arg3152Trp) variant should be considered in the context of an individual’s other genetic findings. At this time, we classify it as a variant of uncertain significance. |