Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793254 | SCV000932600 | likely pathogenic | not provided | 2019-08-09 | criteria provided, single submitter | clinical testing | 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. 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. 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. 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). This variant is present in population databases (rs121908483, ExAC 0.002%). 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. |
| OMIM | RCV000006140 | SCV000026322 | pathogenic | Cystinuria | 1999-09-01 | no assertion criteria provided | literature only |