Submissions for variant NM_033163.5(FGF8):c.318del (p.Glu107fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003332886	SCV004040403	likely pathogenic	not provided	2025-03-27	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 138 amino acids are replaced with 32 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV003332886	SCV004322145	pathogenic	not provided	2023-09-08	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FGF8-related conditions. This variant disrupts a region of the FGF8 protein in which other variant(s) (p.Arg129Pro) have been determined to be pathogenic (Invitae). 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. This sequence change creates a premature translational stop signal (p.Glu107Argfs*33) in the FGF8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the FGF8 protein.