ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.917A>G (p.Tyr306Cys)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002450027 SCV002683262 uncertain significance Cardiovascular phenotype 2021-12-08 criteria provided, single submitter clinical testing The p.Y306C variant (also known as c.917A>G), located in coding exon 7 of the FKTN gene, results from an A to G substitution at nucleotide position 917. The tyrosine at codon 306 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported as homozygous in an individual with concerns for muscular dystrophy that included dilated cardiomyopathy and proximal muscle weakness (Riisager M et al. Neuromuscul Disord, 2013 Jul;23:562-7). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003100113 SCV003440939 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-10-13 criteria provided, single submitter clinical testing 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 disruptive. 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. This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 23746544). This variant is present in population databases (rs771679473, gnomAD 0.004%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the FKTN protein (p.Tyr306Cys).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.