ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.1048G>A (p.Glu350Lys)

gnomAD frequency: 0.00001  dbSNP: rs750759323
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002009155 SCV002273884 uncertain significance Walker-Warburg congenital muscular dystrophy 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 350 of the FKTN protein (p.Glu350Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs750759323, ExAC 0.002%). This variant has not been reported in the literature in individuals with FKTN-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV004616940 SCV005118163 uncertain significance Cardiovascular phenotype 2024-04-28 criteria provided, single submitter clinical testing The p.E350K variant (also known as c.1048G>A), located in coding exon 8 of the FKTN gene, results from a G to A substitution at nucleotide position 1048. The glutamic acid at codon 350 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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