Submissions for variant NM_001079802.2(FKTN):c.1186A>C (p.Lys396Gln)

gnomAD frequency: 0.00001  dbSNP: rs1477740717

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000516301	SCV000613312	uncertain significance	not specified	2017-06-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000767062	SCV000620728	uncertain significance	not provided	2019-10-10	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001359447	SCV001555318	uncertain significance	Walker-Warburg congenital muscular dystrophy	2024-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 396 of the FKTN protein (p.Lys396Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 447339). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FKTN protein function. 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	RCV002341207	SCV002638036	uncertain significance	Cardiovascular phenotype	2023-09-07	criteria provided, single submitter	clinical testing	The p.K396Q variant (also known as c.1186A>C), located in coding exon 9 of the FKTN gene, results from an A to C substitution at nucleotide position 1186. The lysine at codon 396 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000516301	SCV005039666	uncertain significance	not specified	2024-03-30	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000767062	SCV005410781	uncertain significance	not provided	2024-08-19	criteria provided, single submitter	clinical testing	PM2
Fulgent Genetics, Fulgent Genetics	RCV005049584	SCV005679641	uncertain significance	Dilated cardiomyopathy 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Autosomal recessive limb-girdle muscular dystrophy type 2M; Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4	2024-04-30	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001359447	SCV002081976	uncertain significance	Walker-Warburg congenital muscular dystrophy	2021-01-23	no assertion criteria provided	clinical testing