ClinVar

Description

The KEL p.Pro326Gln variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs751284993) and in control databases in 1 of 251308 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 1 of 113610 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Pro326 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 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.