Submissions for variant NM_001079802.2(FKTN):c.374G>T (p.Gly125Val) (rs142783718)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000339279	SCV000341992	uncertain significance	not provided	2017-05-05	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000261037	SCV000476419	uncertain significance	Dilated cardiomyopathy 1X	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina	RCV000318693	SCV000476420	uncertain significance	Fukuyama congenital muscular dystrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000465197	SCV000546096	uncertain significance	Walker-Warburg congenital muscular dystrophy	2019-11-21	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with valine at codon 125 of the FKTN protein (p.Gly125Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs142783718, ExAC 0.02%). This variant has been reported in an infant affected with anophthalmia/microphthalmia or coloboma (PMID: 26130484). ClinVar contains an entry for this variant (Variation ID: 288016). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and in an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000617672	SCV000737183	uncertain significance	Cardiovascular phenotype	2016-10-21	criteria provided, single submitter	clinical testing	Insufficient evidence