Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000793254 | SCV000932600 | likely pathogenic | not provided | 2019-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 259 of the SLC7A9 protein (p.Gly259Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs121908483, ExAC 0.002%). This variant has been observed in individuals affected with cystinuria (PMID: 10471498, 19782624, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 5784). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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, |
RCV000006140 | SCV005654710 | likely pathogenic | Cystinuria | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000006140 | SCV000026322 | pathogenic | Cystinuria | 1999-09-01 | no assertion criteria provided | literature only |