Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544448 | SCV000623547 | uncertain significance | Hypertrophic cardiomyopathy | 2017-05-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 74 of the MYBPC3 protein (p.Ala74Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. In summary, this variant has uncertain impact on MYBPC3 function. The available evidence is currently insufficient to determine its role 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 a MYBPC3-related disease. This variant is not present in population databases (ExAC no frequency). |