ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.647G>A (p.Arg216Lys)

dbSNP: rs1828504500
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001227979 SCV001400360 uncertain significance Walker-Warburg congenital muscular dystrophy 2021-10-08 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. This variant has not been reported in the literature in individuals affected with FKTN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 216 of the FKTN protein (p.Arg216Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon.
Ambry Genetics RCV003294093 SCV004001240 uncertain significance Cardiovascular phenotype 2023-05-16 criteria provided, single submitter clinical testing The p.R216K variant (also known as c.647G>A), located in coding exon 4 of the FKTN gene, results from a G to A substitution at nucleotide position 647. The arginine at codon 216 is replaced by lysine, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 4 and may have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. This amino acid position is well conserved in available vertebrate species. In addition, as a missense substitution this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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