ClinVar

Description

The STK11 p.Asn119Asp variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (rs545015076) as “with uncertain significance allele” and ClinVar (classified as uncertain significance by Invitae, Ambry Genetics and Color). The variant was identified in control databases in 11 of 249,110 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 10 of 30,600 chromosomes (freq: 0.0003, decreasing the likelihood that this variant has clinical significance) and Other in 1 of 6048 chromosomes (freq: 0.0002), but it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, Finnish or European populations. The p.Asn119 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out 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.