Submissions for variant NM_000130.5(F5):c.3799del (p.Leu1267fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003596841	SCV004293798	pathogenic	Congenital factor V deficiency	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu1267Phefs*21) in the F5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F5 are known to be pathogenic (PMID: 30924984). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with factor V deficiency (PMID: 17145618). This variant is also known as g.52162delC, c.3888delC, FS1259ter . For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV004546801	SCV005042852	likely pathogenic	Pregnancy loss, recurrent, susceptibility to, 1		criteria provided, single submitter	clinical testing	The frameshift c.3799delp.Leu1267PhefsTer21 variant in F5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0% in the gnomAD Exomes and novel in 1000 Genomes. This variant causes a frameshift starting with codon Leucine 1267, changes this amino acid to Phenylalanine residue, and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Leu1267PhefsTer21. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.