Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000614279 | SCV000731414 | uncertain significance | not specified | 2017-01-11 | criteria provided, single submitter | clinical testing | The p.Lys99Thr variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy. Data from large population studies is insufficient to asse ss the frequency of this variant. This variant was predicted to be benign using a computational tool clinically validated by our laboratory. This tool's benign prediction is estimated to be correct 89% of the time (Jordan 2011). In summary , the clinical significance of the p.Lys99Thr variant is uncertain. |
Invitae | RCV001046923 | SCV001210848 | uncertain significance | Hypertrophic cardiomyopathy | 2019-11-26 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 517237). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces lysine with threonine at codon 99 of the MYBPC3 protein (p.Lys99Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine. |