rs369742878

Description

The TRPM1 c.2998C>T (p.Arg1000Ter) variant is a stop-gained variant that is predicted to cause premature truncation of the protein. The p.Arg1000Ter variant has been reported in a compound heterozygous state with a second variant in one individual with congenital stationary night blindness type 1C (van Huet et al. 2015). Control data are unavailable for this variant, which is reported at a frequency of 0.000150 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the limited evidence and potential impact of stop-gained variants, the p.Arg1000Ter variant is classified as uncertain clinical significance but suspicious for pathogenicity for autosomal recessive congenital stationary night blindness. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

This sequence change creates a premature translational stop signal (p.Arg1000*) in the TRPM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRPM1 are known to be pathogenic (PMID: 19896113, 19966281, 20300565). This variant is present in population databases (rs369742878, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with TRPM1-related conditions (PMID: 25999674). ClinVar contains an entry for this variant (Variation ID: 167748). For these reasons, this variant has been classified as Pathogenic.