Submissions for variant NM_001079802.2(FKTN):c.703C>A (p.Pro235Thr)

gnomAD frequency: 0.00003  dbSNP: rs373418195

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726450	SCV000344724	uncertain significance	not provided	2016-08-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000726450	SCV000573417	uncertain significance	not provided	2021-11-23	criteria provided, single submitter	clinical testing	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; This variant is associated with the following publications: (PMID: 30564623)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000700000	SCV000828735	likely benign	Walker-Warburg congenital muscular dystrophy	2025-01-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002229751	SCV002511750	uncertain significance	not specified	2022-04-11	criteria provided, single submitter	clinical testing	Variant summary: FKTN c.703C>A (p.Pro235Thr) results in a non-conservative amino acid change located in the Ribitol-5-phosphate transferase FKTN, N-terminal domain (IPR045587) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251280 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in FKTN causing Dilated Cardiomyopathy (0.00011 vs 0.004), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.703C>A in individuals affected with Dilated Cardiomyopathy/FKTN-related disease and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000726450	SCV002541006	uncertain significance	not provided	2021-11-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002480051	SCV002782681	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 with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4	2021-07-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726450	SCV003917685	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000700000	SCV002079592	uncertain significance	Walker-Warburg congenital muscular dystrophy	2020-01-23	no assertion criteria provided	clinical testing