ClinVar

Description

The RP1 p.Leu1417Pro variant was identified in the literature in three patients with retinitis pigmentosa (Simpson_2010_ PMID:21147909; Berson_2001_PMID:11527933). The variant was identified in dbSNP (ID: rs139294220) but was not identified in ClinVar. The variant was identified in control databases in 383 of 281894 chromosomes at a frequency of 0.001359 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 291 of 128722 chromosomes (freq: 0.002261), Latino in 47 of 35418 chromosomes (freq: 0.001327), Other in 8 of 7168 chromosomes (freq: 0.001116), Ashkenazi Jewish in 9 of 10352 chromosomes (freq: 0.000869), European (Finnish) in 19 of 25094 chromosomes (freq: 0.000757), African in 8 of 24592 chromosomes (freq: 0.000325) and South Asian in 1 of 30602 chromosomes (freq: 0.000033), but was not observed in the East Asian population. The p.Leu1417 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.