Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Clinical Genetics, |
RCV002226837 | SCV002505719 | uncertain significance | Hypercalcemia, infantile, 2 | 2021-08-01 | criteria provided, single submitter | clinical testing | |
| Arcensus | RCV002466279 | SCV002564573 | likely pathogenic | Hypophosphatemic nephrolithiasis/osteoporosis 1 | 2013-02-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003089212 | SCV002996478 | likely pathogenic | not provided | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 8 of the SLC34A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC34A1 are known to be pathogenic (PMID: 26047794). This variant is present in population databases (rs754825865, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SLC34A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1679240). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV002226837 | SCV005329300 | likely pathogenic | Hypercalcemia, infantile, 2 | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed invariant splice acceptor c.937-2A>C has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with an allele frequency of 0.008% in gnomAD Exomes database. This variant has been reported to the ClinVar database as Uncertain Significance/Likely pathogenic. SpliceAI predicts this variant to cause splice acceptor Loss (0.94) and splice acceptor gain (0.18). Loss of function variants have been previously reported to be disease causing (Schlingmann KP, et. al., 2016). For these reasons, this variant has been classified as Likely Pathogenic. In absence of another reportable variant in SLC34A1 gene, the molecular diagnosis is not confirmed. |