Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000348762 | SCV000372982 | likely pathogenic | Dalmatian hypouricemia | 2017-04-27 | criteria provided, single submitter | clinical testing | The SLC22A12 c.1145A>T (p.Gln382Leu) missense variant has been reported in two studies in which it is found in a compound heterozygous state in two individuals with renal hypouricemia, and in a heterozygous state in three unaffected family members (Ichida et al. 2004; Wakida et al. 2005). The p.Gln382Leu variant was absent from 75 controls and is reported at a frequency of 0.00093 in the East Asian population of the Exome Aggregation Consortium. Functional studies in Xenopus oocytes demonstrated that the p.Gln382Leu variant significantly decreased urate transport compared to wild type SLC22A12 (Ichida et al. 2004; Wakida et al. 2005). Based on the evidence, the p.Gln382Leu variant is classified as likely pathogenic for renal hypouricemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Revvity Omics, |
RCV000348762 | SCV002022596 | likely pathogenic | Dalmatian hypouricemia | 2020-02-26 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000348762 | SCV002780531 | likely pathogenic | Dalmatian hypouricemia | 2022-05-09 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003409469 | SCV004113069 | likely pathogenic | SLC22A12-related condition | 2023-01-17 | criteria provided, single submitter | clinical testing | The SLC22A12 c.1145A>T variant is predicted to result in the amino acid substitution p.Gln382Leu. This variant was reported to be causative for renal hypouricemia (Ichida et al. 2004. PubMed ID: 14694169; Lam et al. 2008. PubMed ID: 18760270; Zhou et al. 2019. PubMed ID: 31131560). Functional studies showed that this variant impairs the transport efficiency (Ichida et al. 2004. PubMed ID: 14694169; Toyoda et al. 2021. PubMed ID: 33821957). This variant is reported in 0.15% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-64367222-A-T). This variant is interpreted as likely pathogenic. |
| Invitae | RCV003546509 | SCV004273958 | pathogenic | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 382 of the SLC22A12 protein (p.Gln382Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hypouricemia (PMID: 14694169, 15634722, 30097038, 31131560, 31591475). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 305239). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SLC22A12 function (PMID: 14694169, 15634722). For these reasons, this variant has been classified as Pathogenic. |