Submissions for variant NM_001079802.2(FKTN):c.58T>G (p.Phe20Val)

dbSNP: rs1554731003

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000538044	SCV000630820	uncertain significance	Walker-Warburg congenital muscular dystrophy	2024-02-17	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 20 of the FKTN protein (p.Phe20Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with LBBB, PVC, atrial fibrillation, nonischemic cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 459222). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FKTN protein function with a negative predictive value of 80%. 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.
Eurofins Ntd Llc (ga)	RCV000730719	SCV000858480	uncertain significance	not provided	2017-12-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000730719	SCV002003652	uncertain significance	not provided	2021-04-06	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Revvity Omics, Revvity	RCV000730719	SCV003832678	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004619323	SCV005118148	uncertain significance	Cardiovascular phenotype	2024-03-16	criteria provided, single submitter	clinical testing	The p.F20V variant (also known as c.58T>G), located in coding exon 1 of the FKTN gene, results from a T to G substitution at nucleotide position 58. The phenylalanine at codon 20 is replaced by valine, an amino acid with highly 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 alteration remains unclear.