ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.1046T>C (p.Val349Ala)

gnomAD frequency: 0.00002  dbSNP: rs539089647
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519404 SCV000619897 uncertain significance not provided 2017-08-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FKTN gene. The V349A variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, V349A is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Labcorp Genetics (formerly Invitae), Labcorp RCV000634053 SCV000755331 uncertain significance Walker-Warburg congenital muscular dystrophy 2021-11-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 349 of the FKTN protein (p.Val349Ala). This variant is present in population databases (rs539089647, gnomAD 0.01%). 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: 451226). 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.
Ambry Genetics RCV002404346 SCV002704102 uncertain significance Cardiovascular phenotype 2018-08-02 criteria provided, single submitter clinical testing The p.V349A variant (also known as c.1046T>C), located in coding exon 8 of the FKTN gene, results from a T to C substitution at nucleotide position 1046. The valine at codon 349 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly 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.

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