Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV001799071 | SCV002042606 | uncertain significance | Cardiomyopathy | 2020-12-08 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001356691 | SCV001551930 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The TTN p.Lys205Glu variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs763768455) and in control databases in 2 of 251176 chromosomes at a frequency of 0.000007963 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 1 of 34584 chromosomes (freq: 0.000029) and European (non-Finnish) in 1 of 113548 chromosomes (freq: 0.000009), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Lys205 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. |