ClinVar

Description

The SLC34A1 c.458G>T (p.Gly153Val) missense variant has been reported in two studies and is found in a total of three individuals affected with either idiopathic infantile hypercalcemia or hypophosphatemia (Schlingmann et al. 2016; Braun et al. 2016). The three affected individuals include each in a homozygous, compound heterozygous, and heterozygous state. The p.Gly153Val variant was absent from 204 controls and is reported at a frequency of 0.000045 in the European (non-Finnish) population of the Genome Aggregation Database. Functional analysis in Xenopus oocytes showed that wildtype protein induced significant uptake of labeled phosphate, whereas the p.Gly153Val variant did not induce uptake significantly different from that of noninjected control cells. Transiently transfected opossum kidney cells showed complete intracellular retention of mutant protein with no detectable actin colocalization, in contrast to the wild type protein, which localized at the plasma membrane and colocalized with actin (Schlingmann et al. 2016). Based on the collective evidence, the p.Gly153Val variant is classified as likely pathogenic for SLC34A1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.