ClinVar

Description

The SLC36A2 p.Met205Val 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: rs143611303) and in control databases in 37 of 282824 chromosomes at a frequency of 0.000131 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 33 of 129140 chromosomes (freq: 0.000256), European (Finnish) in 2 of 25120 chromosomes (freq: 0.00008) and Latino in 2 of 35436 chromosomes (freq: 0.000056), while the variant was not observed in the African, Ashkenazi Jewish, East Asian, Other, and South Asian populations. The p.Met205 residue is 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.