Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003064572 | SCV003443228 | likely pathogenic | not provided | 2022-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 73 of the SLC7A9 protein (p.Gly73Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of cystinuria (PMID: 23532419; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
| Fulgent Genetics, |
RCV005028143 | SCV005654746 | uncertain significance | Cystinuria | 2024-06-03 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003418723 | SCV004116250 | uncertain significance | SLC7A9-related disorder | 2024-09-12 | no assertion criteria provided | clinical testing | The SLC7A9 c.217G>A variant is predicted to result in the amino acid substitution p.Gly73Arg. This variant was reported in at least two unrelated individuals with cystinuria; however, pathogenicity was not established (Popovska-Jankovic K et al 2012. PubMed ID: 23532419; Case 7 in Jeong et al. 2023. PubMed ID:37893120). In at least one of these reported cases the variant was not found with a second SLC7A9 variant (Jeong et al. 2023. PubMed ID:37893120). At PreventionGenetics, we have observed the c.217G>A variant with a second SLC7A9 pathogenic frameshift variant in an individual with cystinuria (internal data). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect this variant could be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |