Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779454 | SCV000916079 | uncertain significance | Hypouricemia, renal, 2 | 2017-04-28 | criteria provided, single submitter | clinical testing | The SLC2A9 c.512G>A (p.Arg171His) missense variant has been reported in a homozygous state in one symptomatic individual with renal hypouricemia (Windpessl et al. 2016). This individual's sister was also homozygous for the variant and was asymptomatic, but exhibited very low serum uric acid levels. The individual's unaffected mother and another sister were heterozygous for the variant and had normal serum uric acid levels. Of note, some individuals with this condition may not have symptoms whereas other individuals with the condition experience kidney problems or have symptoms after strenuous exercise. Control data are not available for the p.Arg171His variant, which has been reported at a frequency of 0.0001 in the African population from the Exome Aggregation Consortium, however this is based on one allele in a region of good sequence coverage so the variant is predicted to be rare. Another variant at the same position (p.Arg171Cys) has been reported in a homozygous state in three siblings from a consanguineous family with renal hypouricemia (Dinour et al. 2012). In functional studies, that variant was shown to have reduced uric acid transport activity. The evidence for the p.Arg171His variant is limited. The p.Arg171His variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for renal hypouricemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |