ClinVar

Description

The MYH7 p.Arg1289Trp variant was not identified in the literature but was identified in dbSNP (ID: rs180824037) and ClinVar (classified as uncertain significance by Knight Diagnostic Laboratories, Oregon Health and Sciences University). The variant was identified in control databases in 3 of 251474 chromosomes at a frequency of 0.00001193 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 3 of 113758 chromosomes (freq: 0.000026), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Arg1289 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume 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.