ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.755A>T (p.Tyr252Phe)

gnomAD frequency: 0.00001  dbSNP: rs574626895
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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 RCV001363186 SCV001559287 uncertain significance Walker-Warburg congenital muscular dystrophy 2022-04-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 252 of the FKTN protein (p.Tyr252Phe). This variant is present in population databases (rs574626895, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1054641). 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 phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV002395810 SCV002675201 uncertain significance Cardiovascular phenotype 2024-09-25 criteria provided, single submitter clinical testing The p.Y252F variant (also known as c.755A>T), located in coding exon 5 of the FKTN gene, results from an A to T substitution at nucleotide position 755. The tyrosine at codon 252 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, phenylalanine is the reference amino acid in other vertebrate species. In addition, 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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