Submissions for variant NM_001079802.2(FKTN):c.536G>C (p.Arg179Thr)

dbSNP: rs119463994

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000441410	SCV000520899	likely pathogenic	not provided	2016-12-19	criteria provided, single submitter	clinical testing	The R179T variant in the FKTN gene has been reported previously in the heterozygous state in individuals with Fukuyama congenital muscular dystrophy who were also heterozygous for the common insertion in the 3' untranslated region of FKTN; however, phase was not proven in most of these individuals and in vitro functional studies were not included (Murakami et al., 2006; Amiya et al., 2016). Cardiomyopathy was the primary presenting feature in all individuals; muscular, cognitive, neurological, and ocular abnormalities were minimal or absent (Murakami et al., 2006; Amiya et al., 2016). The R179T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R179T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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. The R179T variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002512702	SCV003441389	uncertain significance	Walker-Warburg congenital muscular dystrophy	2022-05-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 179 of the FKTN protein (p.Arg179Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FKTN-related conditions (PMID: 17036286, 27521547). ClinVar contains an entry for this variant (Variation ID: 3210). 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 expected to disrupt 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.
Baylor Genetics	RCV000003365	SCV004199746	pathogenic	Dilated cardiomyopathy 1X	2023-04-22	criteria provided, single submitter	clinical testing
OMIM	RCV000003365	SCV000023523	pathogenic	Dilated cardiomyopathy 1X	2006-11-01	no assertion criteria provided	literature only