Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Clinical Services Laboratory, |
RCV000357115 | SCV000476421 | uncertain significance | Dilated Cardiomyopathy, Recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000264741 | SCV000476422 | uncertain significance | Fukuyama congenital muscular dystrophy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000634069 | SCV000755347 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2019-05-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 133 of the FKTN protein (p.Met133Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs569778463, ExAC 0.2%). This variant has not been reported in the literature in individuals with FKTN-related disease. 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. A different missense substitution at this codon (p.Met133Thr) has been reported in an individual affected with Fukuyama-type congenital muscular dystrophy (PMID: 17597323). 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. |