Submissions for variant NM_001079802.2(FKTN):c.22G>T (p.Val8Leu)

dbSNP: rs368981218

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000253874	SCV000319876	uncertain significance	Cardiovascular phenotype	2023-09-19	criteria provided, single submitter	clinical testing	The p.V8L variant (also known as c.22G>T), located in coding exon 1 of the FKTN gene, results from a G to T substitution at nucleotide position 22. The valine at codon 8 is replaced by leucine, an amino acid with highly similar properties. In one cohort study, this variant was reported in one individual with dilated cardiomyopathy and in one control participant (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000472415	SCV000546094	likely benign	Walker-Warburg congenital muscular dystrophy	2024-12-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000519772	SCV000619594	uncertain significance	not provided	2017-07-31	criteria provided, single submitter	clinical testing	The V8L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V8L 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 variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Revvity Omics, Revvity	RCV000519772	SCV003832668	uncertain significance	not provided	2020-02-20	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000519772	SCV001932433	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000519772	SCV001973923	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000472415	SCV002078732	uncertain significance	Walker-Warburg congenital muscular dystrophy	2020-02-12	no assertion criteria provided	clinical testing