Submissions for variant NM_206965.2(FTCD):c.1366dup (p.Glu456fs)

dbSNP: rs777099958

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174355	SCV000225641	pathogenic	not provided	2014-08-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000174355	SCV001153596	uncertain significance	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Invitae	RCV001199937	SCV001408987	pathogenic	Glutamate formiminotransferase deficiency	2023-11-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu456Glyfs*56) in the FTCD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 86 amino acid(s) of the FTCD protein. This variant is present in population databases (rs777099958, gnomAD 0.5%). This premature translational stop signal has been observed in individual(s) with glutamate formiminotransferase deficiency (PMID: 29178637, 30740726). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 194078). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the FTCD protein in which other variant(s) (p.Leu536*) have been determined to be pathogenic (PMID: 29178637, 30740726). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002516627	SCV003733085	pathogenic	Inborn genetic diseases	2022-06-10	criteria provided, single submitter	clinical testing	The c.1366dupG (p.E456Gfs*56) alteration, located in exon 12 (coding exon 12) of the FTCD gene, consists of a duplication of G at position 1366, causing a translational frameshift with a predicted alternate stop codon after 56 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been reported in the compound heterozygous state with a second FTCD alteration in patients with glutamate formiminotransferase deficiency (Majumdar, 2017). Based on the available evidence, this alteration is classified as pathogenic.
GeneDx	RCV000174355	SCV003798750	likely pathogenic	not provided	2022-07-06	criteria provided, single submitter	clinical testing	Observed with a pathogenic variant in a patient and observed with a variant of uncertain significance in a patient in the published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Ahrens-Nicklas et al., 2019); Frameshift variant predicted to result in protein truncation, as the last 86 amino acids are replaced with 55 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 31980526, 24077912, 30740726, 29178637)
OMIM	RCV001199937	SCV001370724	pathogenic	Glutamate formiminotransferase deficiency	2022-06-17	no assertion criteria provided	literature only