ClinVar

Description

The FLNC p.Val1793Met variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs587780337) and ClinVar (classified as a VUS by Genetic Services Laboratory, University of Chicago) The variant was also identified in control databases in 17 of 280620 chromosomes at a frequency of 0.000061 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 16 of 35362 chromosomes (freq: 0.000453) and Other in 1 of 7148 chromosomes (freq: 0.00014), while the variant was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish) or South Asian populations. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE) do not predict a change in splicing at the variant location. The p.Val1793 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. 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.