Submissions for variant NM_206965.2(FTCD):c.1358C>T (p.Thr453Met)

gnomAD frequency: 0.00075  dbSNP: rs200283734

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000191087	SCV000245483	uncertain significance	Glutamate formiminotransferase deficiency		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000191087	SCV000820206	uncertain significance	Glutamate formiminotransferase deficiency	2024-10-30	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 453 of the FTCD protein (p.Thr453Met). This variant is present in population databases (rs200283734, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FTCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 209155). 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) indicates that this missense variant is not expected to disrupt FTCD protein function with a negative predictive value of 80%. 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	RCV002517909	SCV003598530	uncertain significance	Inborn genetic diseases	2021-02-22	criteria provided, single submitter	clinical testing	The c.1358C>T (p.T453M) alteration is located in exon 12 (coding exon 12) of the FTCD gene. This alteration results from a C to T substitution at nucleotide position 1358, causing the threonine (T) at amino acid position 453 to be replaced by a methionine (M). The p.T453M alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV003436983	SCV004151975	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	FTCD: BP4
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001251767	SCV001427509	uncertain significance	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing